# Men's Hair Loss > Hair Loss Treatments > Cutting Edge / Future Treatments >  I think I've hacked it

## FGF11

I was not aware that there a lot of these forums, however, I previously posted some comments on a blog that explained hastily about my progress. Now, what I am about to write here, is a one person experiment, and may or may not work on other people. It should also be noted that, since, it was EXTREMELY expensive to follow this protocol, I just did the whole experiment on a small area, on my temples. I've started this about a month ago, and have been able, to grow hair, in a size about a bit less than 1cm*1cm. Therefore, if you are financially capable of doing this, you might have a very effective treatment. HOWEVER, I DO NOT SUGGEST DOING ANY OF THIS. Unless, experimental and with full knowledge. 

So let me explain a little about what I have been able to find:

This, to my knowledge, (I have done extensive reading on the subject), is the first time that this THEORY is mentioned, and it is completely my own. Although, I have proven that this works, it still is a THEORY, so take it with a grain of salt. I am also a life scientist.

This text is also a bit technical, so maybe a few people, could grasp the idea fully. If you don't UNDERSTAND it, though, please don't say that it's bad things, and just stop reading now, and keep a positive attitude. I have no agenda to gain from this, and I'm only doing this to spread words and knowledge, and may someone can try this in larger scale that I did.

This is mostly related to Common Patterned Baldness, however, it can, potentially treat alopecia areata as well. 

I appreciate, however, if you add educated knowledge into this post.

Anyways, Here is what I did and why I did it:

I think many of you already know that hair follicles have a paradoxical appearance in development. We are born with a hair (Lanugo) that is fuzzy and then it falls down and a terminal hair is grown replacing it. At this stage most of the body, do not have hair shafts. Even though, they, have fully formed hair follicles, that are dormant. Eventually, with puberty though, hair follicles and some other cells of the body (for example, Epiphyseal plates) are told to act differently, and change their nature. This happens mostly as a response to hormonal changes.

For example, hormonal changes in women, (Estrogen) cause a second growth of mammary glands. You will be amazed to know that mammary glands are basically VERY VERY similar to hair follicles. In fact, the way they grow, is by invagination of epithelial layer of skin into the fat pad of the mammary gland, and in the process signalling creation of adipocytes, just like, hair follicles and sebaceous glands. Estrogen Receptor by the way is quite similar to Androgen Receptor.

Anyways, in males, Inactive follicles (lets call them dormant), are activated by a signal (testosterone and DHT) to produce hair shaft and grow (just like mammary glands). Its very important to know that during development hair follicles are originated from different populations. For example, dermal part of the hair follicles on the head come from a different part in development than in the body. Their nature is so different they can be quite different physiologically than follicles from the body. This is the main reason Body hair transplantation will not work, and never will. Because these follicles are developmentally different.

Its very important to know that during development hair follicles are originated from different populations. For example, dermal part of the hair follicles on the head come from a different part (neural crest cells) in development than those fibroblast in the body. Their nature is so different they can be quite different physiologically than follicles from the body. This is the main reason Body Hair Transplantation will not work, and never will. Because these follicles are developmentally different.

Now back to hair loss, some males are susceptible to hair loss, this is highly based the person's genetic background and almost environment plays no rule. 

It was found out that people who are castrated early on (before puberty hits) will never go bald. Actually I think Hippocrates found this out. Long Long time ago. Basically, sine these people dont produce testosterone, they can't have DHT and they don't go bald. This however, is not quite right. As testosterone, in small quantities, can be made elsewhere, maybe in adrenal glans (I think!). So they basically CAN go bald, but, since their population has always been so small and they have low testosterone they won't go bald. 

There is one other condition, call androgen insensitivity syndrome. Now, these people also dont go bald, these people, in contrast to castrated people, have usually a mutation (more than 400 known mutations are there) in their Androgen Receptor (AR) gene. Many of these mutations dont let these Androgen Receptor genes to get into the nucleus and transcribe a set of genes that can cause baldness (or hair pubical or facial hair growth). 

So even though they might be prone to baldness, they do not go bald. (imagine introducing a normal AR gene in their nucleus, they will go bald if they have the genetics back ground for it, this experiment would be like the original experiment of injecting testosterone in Castrated People).

Now another population was identified that they also did not go bald, and they were people who did not have 5-alpha reductase gene (or some mutations in it that made this gene not active), and so these people also did not go bald. As you know, 5-alpha reductase converts Testosterone (TT) to Dehydrotestestrone (DHT), these people also had a smaller Prostate (like the other two populations), so Pharma got interested and stepped in to make a product. They basically cultured a basic cell type, and added thousands of different chemicals to these cells, to see which one, inhibits DHT production and boo, finasteride was born. It was easy to get finasteride approved because it was already approved for benign prostate hyperplasia, that's one reason finasteride is there and other anti-androgen are not here. IT WAS EASIER TO GET AN APPROVED DRUG APPROVED FOR ANOTER DISORDER!

With Finasteride, however, androgen receptor is still able to bind other hormones and get into the cells (like testosterone). Interestingly, no matter how much people increased the dose of Finasteride, it never reversed hair loss in significant proportions, in already miniaturized hair follicles. 

Even castration of people did not help hair follicles to come back to life. This was very disappointing for big pharma, they jumped around like idiots, and they did not know what to do. SO THEY GAVE UP, and that's why mostly smaller START-UPs are trying to get into the game.

Before propecia, another drug, minoxidil also was approved that no one had any idea how it increased hair numbers and how it made some hairs to go terminal. Some said K changes, some said, more blood, some said nutrition. However, I will get back to Minoxidil.

Anyways, researchers, still did not know what to do, and so they started to look deeper.

They started to look into stem cells, of the hair follicles. Now, these stem cells are adult stem cells, a set of cells that dont divide often and when they do, they create one cell (progenitor cell) that can divide so fast producing a set of other cells ( Transit amplifying cells) that can differentiate to cells of the hair follicle (for example dermal papillae or matrix cells [which is epithelial]). 

Scientists found out that, hey, hair follicles are alive in the bald scalp and they have the stem cells but they are just not activated, and they lack the signal to call them to get activated. This was interesting, and it made the birth for many companies. 

There were a set of signals known to activate adult stem cells, of these, WNT signals were the best known. However, the way these signals work needs a decade more research, there dozens of WNT molecules, and each of them gets modified in dozens of ways and each cells have dozens of receptors for these WNT molecules and each of those receptors bind dozens of other receptors (co-receptors) that each can have dozens of different responses, and each of these responses can act synergistically, or separately. 

So we are far from understanding these signalling pathways, and secretion molecules.

There are now, a set of different signalling pathways, like BMP, SHH, FGF, an so on. Anyways, however, some companies tried to mimic these pathways but it will never work out for the simple fact that that it is complex, an no constitutive activation of one signalling pathway (as it is a secondary response) will cause complete activation.

Imagine, you want to tell an asian to go buy you a certain flower and come back home with that flower and put it in the right jar next to a window. Now, you know certain words, when you through those words out, you will have some effect on this Chinese girl (who dont understand english) but you will never be able to exactly tell this girl by saying some words randomly, or even mimicking some words you've head else wear (like walk) in for example by watching TV shows (other adult stem cells, the technology of Samumed or Histogen) to go and do this complex process, this is just too complex. So any technology or company pursuing secondary signals is doomed to fail, because its impossible as of now to know the signals.

I dont get much into details, however, take my word for granted when I say cloning hair follicles is also not possible any time soon. We are FAR FAR from that. Any company claiming that it is near is LYING, through away Replicel, aderans, intercytex, and other companies that say they will do that. They wont. Its possible but it takes a long time to learn the signals. To learn when to add BMP, when to add WNT, when to add FBS. When to co-culture with Keratinocytes, when not to. So it needs tons of research, and no single company is capable of doing this. 

Anyway, getting back, to research. From time to time, some factors where shown to be involved in hair follicles. Some pathways, some kinases, some proteins, some inhibitors, they made hair follicles grow, they made them shrink. 

But these factors were also so confusing, and almost no one knew what was going on. They still don't. It was hard to make sense of these factors. For examples, it was known that TGF-Beta makes hair shrink and go to Catagen, no longer staying long enough in anagen to produce hair shafts.

IL-6 ( a cytokine increased in hairless scalp, like PGD2) is shown to cause hair follicle to shrink. 

WNTs caused hair follicles to grow, they activated beta-catenin but how was it making its effect. Why minoxidil had some effect? Why Arthritis drugs were effective? What was the role of immune system? What were cytokines doing in the hair follicle, and how did they affected hair follicles.

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## FGF11

So about 5 months ago, I started to read almost every paper and PUBLICATION I could get my hands on. I read about hair follicles, adult stem cells, hair cloning, hair immune system, … and here is how I found all the connections and patterns, and led it me to develop a theory that could potentially grow hair. 

Once again, publishing this here, does not mean, it’s not true [It also does not mean it's true], so once again take it with a grain of salt. I am pro open science, so that’s why I am writing it here.  Also don’t think just because you’r reading it here, it’s not original. It’s actually original, and if you look into literature and internet you will not see one person or scientist mentioning this finding that I am about to say.

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## FGF11

Any ways, back to the story, I sat down and tried to think how all these connect, and here is what I found. Some scientists that you hear their names here all the time, have told me that this is highly probable and I might be right. None, I guess, however, has yet found time to test this, as they have to go through papers and grants and stuff to do experiments, and some experiments they can never do. While I was able to do a thoughtful small experiment, That's why I think, we need to do what has happened in Computer Science and bring it to biology, self-driven motivation to make science progress.
However, ONCE AGAIN, please if you don't know what you are reading, NEVER try this, also this is quite EXPENSIVE and, so you needs lots of money to follow it. 

Anyways, It all came to me, when I read about castration-resistant prostate cancer. Thanks to researchers studying Prostate Cancer (PC), the complex biology of Androgen Receptor has been under heavy investigation. This has led to fascinating discoveries regarding AR activation, localization and dynamics. Not only involved in hair loss, AR is also the major deriving force behind malignancy of Prostate Cancer (PC) cells. Among current therapies for PC is the complete inhibition of testosterone production to stop androgen-dependent growth of PC cells. However, in some of the cases, a recurrence of PC will happen by appearance of a set of androgen-independent malignant cells (CRPC). However, these CRPC cells are still AR dependent. This led researchers to further study mechanisms by which AR activation can happen regardless of androgens. Interestingly, it seems some post-translational modification (phosphorylation) of AR is both necessary and sufficient for activation and nuclear localization of AR in an androgen-independent manner. Notably, the role of cytokine receptors (such as IL-6 receptor) is gaining more ground amongst researchers.

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## FGF11

Also I told you earlier about the involvement of Androgen Receptor in male pattern baldness or CMB. Androgen Receptor (AR) is conclusively involved in Common Male Baldness (CMB). Upon binding to androgens, notably dehydrotestestrone (DHT), AR translocates into nucleus to transcribe a set of AR-responsive genes. Finasteride, an FDA approved drug for CMB, inhibits production of DHT by blocking the action of 5 alpha-reductase. However, Finasteride is not capable of inducing hair regrowth in the majority of already miniaturized hair follicles (HFs). Given that an increase in AR levels alone is not the causative agent deriving HF miniaturization, its quite probable that AR nuclear localization and/or cytoplasmic retention and not its increased levels is the cause of CMB. AR is a very complex transcription factor that undergoes multitude of post-translational modifications which dictate its function and dynamics. Interestingly, androgen receptor nuclear localization can occur in an androgen independent manner. In fact, androgen-independent AR nuclear transport and activation is a common phenotype of castration-resistance prostate cancer (CRPC) cells. Here, I propose a unifying theory for the onset and progression of CMB and will tell you how I hacked a small section of my hair loss.

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## FGF11

Recent findings regarding the involvement of cytokines in the progression of CMB, the inability of potent anti-androgens to reverse HF miniaturization, involvement of AR in the malignancy of castration-resistance prostate cancer (CRPC) cells, and paradoxical AR levels observations in facial and scalp hair follicles, led me to develop this unifying theory of CMB. To better understand my theory, I’ll start by explaining these seemingly unrelated factors in the context of AR nuclear localization and will tell you about some key experiments that I did to conclusively test the fidelity of my theory.

Now here is the explanation of my theory: CMB usually beings with observable miniaturization in the vertex and frontal regions of the scalp and progresses forward and backward, respectively. The progression continues until the two miniaturized regions meet one another. Histological studies showed that cytokine levels are increased in the bald scalp of males with advanced CMB compared to haired scalp (occipital regions). This is important as cytokines are involved in AR androgen independent nuclear localization. Cytokines surpassing a threshold level, therefore, can switch miniaturization of HFs from AR-dependent androgen-dependent (ARDAD) to AR-dependent androgen-independent (ARDAI). This, however, has not escaped my mind that ARDAD and ARDAI nuclear localization can synergistically control AR dynamics. This can explain why early administration of Finasteride is extremely more effective. Since, it theoretically can stops ARDAD switch to ARDAI as the dominant AR nuclear localization signal in miniaturized HFs. Once switched, ARDAI HF miniaturization creates an indefinite loop of positive feedback further strengthening its androgen independent nuclear localization. This potential explains pattern formation and progression through involvement of immune cells (cytokine production).

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## FGF11

Recently, pharmacologic inhibition of JAK-STAT signalling pathway by Tofacitinib, has been shown to be involved in early activation HF anagen cycle in mice. Interestingly, in mice AR localizes to nucleus during telogen and catagen but not anagen (in hair bulbs). The binding of Interleukin 6 family of cytokines to its receptor cause STAT3 phosphorylation. Notably, STAT3 phosphorylation is involved in ARDAI nuclear localization in CRPC cells through unknown mechanism(s). This further supports that ARDAI nuclear localization might be involved in miniaturization of HFs.  Other papers have shown that Beta-catenin and androgen receptor also co-localize in cytoplasm, recent findings of Dr. Watt regarding beta-catenin and androgen receptor nuclear transport in anagen and other HF cycles, basically, proves why Samumed or Histogen are seeing some basic regrowth but not much. Their technology might work, but basically they to keep Beta-catenin constantly in the cell nucleus, and it's almost not possible if AR is constantly active, so they WON'T work. When you activate WNT pathway, what you do is you activate beta-catenin, and this causes beta-catenin to get into nucleus, and in unknown process you keep Androgen Receptor out nucleus, proving that their effect might work from Androgen Receptor axis of signalling.

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## FGF11

Basically Setipiprant will not work (or at least I HIGHLY believe so), as there are lots of cytokines that are increased in the hair follicles microenvironment. Like IL-6, TGF-Beta, PGD2, … and so on. An just stopping one, is not going to have an effect. It’s like a domino, you can’t stop the domino, while it’s in the middle you have to stop it from the start. Even if you stop the receptor for PGD2,  what you do is that you cause a build up of PGD2 and subsequently 15d-PGJ2, but the problem is 15d-PGJ2 acts intracellularly, and no receptor has yet been found for 15d-PGJ2. But when you read the paper on PGD2, you see that 15d-PGJ2 is way more detrimental to hair follicles than PGD2, and in a course of 3 days completely blocked the growth rather than 7 days for PGD2. So I’m saying the most effective way is to target L-PGD2 synthase (if at all), as well as PGD2 receptor with Seti. Now since the experiments was done ex vivo, they literally did not include 15d-PGJ2 in their experiments to see if it’s effect can be blocked through GPR-44. So it’s a black hole, one should genetically lower levels of PGD2 synthase, add PGE2 periodically and block GPR-44 to see an effective increase in hair growth. However, again, it's acting as a secondary signal, and it will not work, prostaglandin theory is looking at a small picture and forgetting the large picture.

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## FGF11

Now knowing this I set out to see if individually I can test, whether my theory is true, or not. And It seems after thousands of years, I can say, we have a treatment effective enough that can reverse hair follicle miniaturization with one single simple intervention with no side effects, Yes, I know it seems like a fairy tale, but it’s true ( at least so far). Now, Why I am publishing this here, and I'm not trying to monetize it. It's because, I believe in open science. Something like a Github of biology. Like an open source code for biology. It's hard knowing that FDA, even though, extremely useful, sometimes is on the way. Also another reason, that, I do not want to monetize this, is because this treatment will never be useful for the majority of people. It will be ridiculously expensive, at least until the next ten years or so. So no seed funding venture or angel investor is (or will) likely be interested.

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## FGF11

again, I know this may be a bit hard for lay people to understand, but please read more about it. Okay, so about a month ago, I sat down thinking how can I prove my theory. I had access to most of the inhibitors that I wanted, also I should have paid for it, it was an instant access. (I am lucky). Basically, Androgen receptor inhibitors are three types:

#1 Recently developed pure AR antagonists (non-steroidal), (these include MDV3100, ODM-201, ARN-509 and other safe AR antagonists).

#2 Non-pure non-steroidal AR antagonists such as (such as RH58841 [We know about this], Flutamide, Bicalutamide and many others)

#3 5-alpha reductase inhibitors (finasteride, dutasteride) can cause regrowth. [these are actually not AR antagonists but I brought them here so you know them]

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## FGF11

Based on my theory so far, any of Pure AR non-steroidal antagonists, (these include MDV3100, ODM-201, ARN-509 and other safe AR antagonists) should be able to reverse HF miniaturization (to some extent). ODM-201 should probably be the most effective one, as it doesn't cross blood brain barrier (you won't get brain fog, like finasteride or MDV3100), and also it works on all different types of signalling pathways working on AR, and also has a short half life. And also just because pure antagonists are cancer drugs, it doesn’t mean they are more dangerous than other anti-androgens, You have to look at IC50, and other things, site of actions. Any ways, I say they are not dangerous, but still, I did not have the balls, nor the lack of ethics to try it. It's also very new, so expensive.

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## FGF11

However, the effectiveness of Androgen Antagonists should be as follow: 1) pure 2) non pure and at the last 3) 5 alpha inhibitors. I sat down, and I thought what could be an alternative, and my eureka moment was when I was looking at the my stella beer. Yes! gene therapy seemed like an alternative alternative. I designed an Antisense Oligonucleotide, and blast the sequence to human genome, to make sure it specifically target AR with no off targets. Antisense Oligonucleotide are much cheaper to make than siRNA, so I chose them as my option. Also, once inside the cell, they can remain active for almost a week, Unlike siRNA's.

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## FGF11

There was one big problem though, there was no way to efficiently driver them pass Stratum Corneum. I tried a novel formulae, a cream with the following compositions: glyceryl monostearate (10%), hydroxypropyl methylcellulose (0.5%), isopropyl myristate (10%), methylparaben (0.5%), propylparaben (0.5%), polyoxyl-40-stearate (15%), and water. I stole the formulae from a publication, however, it seemed that this formulae could only deliver Antisense Oligonucleotides, (ASO) into parts with HFs. So It did not seem to be effective at silencing AR gene. I have to say though, to design the AR-ASO, I used a special section of the gene, that seems active in all different splice variants of AR. There are dozens of Splice variants by the way.

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## FGF11

Anyways, I saw almost zero effect, now, ASO technology is extremely expensive. Kynamro patients pay like 250,000 for just one year of treatment, so I was not able to waste a lot of money, so I was only testing this, in 1cm*1cm of my skin, it did not work. I however, believe in the technology, and thought of something else, I injected about 100µl of this ASO ****tail Intradermally, much like a TB test. I say a ****tail of ASO, as I had an ASO targeted to Exon-1 and another ASO targeting Intron-1 on AR. Remember, that I was doing this in a very small area, and chances of it getting systemic was absolute zero, so I was taking all the precautions. Also ASO's in small amount are quick to degrade in circulation, and even if they did go to, the quantity was so small that it was like zero effect (much safer than Finasteride). However, since derm has no blood connection, they accumulate in derma layer, so they will enter the cells. Also, I used a chemical modification that gives them negative charge, so they enter the cells regardless of lipolex (it is a common knowledge), any ways, I injected a bout 1mg/100µl of AR-ASO ****tail, every three days, for one month, in an area (1cm*1cm) that had lost its hair ten years ago. After a month, I saw the hairs coming out. However, I had more than 10 injections with a 31 gauge syringe so the skin needed some time to heal. I was sure that ASO was working, however, it was not proving, whether, this effect could be seen by anti androgens also, so I tried to apply RU58841, in the (1cm*1cm) area, and stopped injection of ASO (which by the way costed me more than 2000$, for a month and only ten injection and for an area of 1cm*1cm). Anyways, applying RU58841, was NOT able to keep the hair, and the hair started to miniaturize.

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## FGF11

Now, please don't get excited. This has the potential to reverse hair follicle miniaturization in areas that have lost hair for a long time, but it's ridiculously expensive, and hard to do (lack of a proper vehicle). Therefore, it's as of now, (may be not in ten years), will not come to the market. However, as a scientist, my curiosity led me to do this. Also, since it's an experiment, that is translational and (with a proven target) it was possible to publish this, but, I prefer to not publish such a thing in a low impact journal, but I prefer not to, as I have much more challenging academic ideas to follow, and prefer not to publish such articles. Also, I think, the world is changing and less and less people try to publish things that are not academically as rewarding as such I mentioned. Although, the academically rewarding publications, in the big three, is still highly sought after. For example read this new, [http://www.nature.com/news/the-bigge...proof-1.18509]. Anyways, I hope this not only helps people get a better understanding of AGA, also gives them the hope that it is possible to Reverse hair follicle miniaturization sometime in future.

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## FGF11

Mark Watney: Every human being has a basic instinct: to help each other out. ... odds, I'm left with only one option, I'm gonna have to science the shit out of this. 

I'll come here from time to time, to answer, well formed thoughtful questions that you might have. Good luck everyone, and enjoy your life.

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## Not giving up

Dude, I'm just going to straight up say what we're all thinking here; You post saying you've found a cure that will regrow hair in a month with no sides, and yet you have no photographical evidence... I want nothing more than all of this to be true, and for you to be some sort of genius finding a miracle cure in your basement, but to convince people you need more than theoretical science jargan, you need evidence. 

Thanks for taking the time to give us all this info though bud, you seem very clued up either way.

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## FGF11

Thank you Not Giving Up. 
I have photographs, but I do not want to publish them for some reasons. Also, I'm not saying I have the cure, or it's the cure with no side effects. I said no side effects, as I tried this in small amounts, it's quite possible to get sides while increasing the oligo concentration. Another thing, I stopped the experiment in one month, so it could have been a small boost to hair growth, and may be it's not a cure. Also, I'm not trying to convince anyone, those who truly understand what I've done, will know that I have no agenda. I just shared what I had done. And also I'm not a genius. 

Thank you for appreciating What I wrote here, it might, someday, come handy, to one person, who knows! take care

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## topt

wow; I need to read it all again; thank you for sharing.
BTW; you dont think finasteride is safe ?

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## Follisket

> and enjoy your life.


 For real?

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## NeedHairASAP

> Mark Watney: Every human being has a basic instinct: to help each other out. ... odds, I'm left with only one option, I'm gonna have to science the shit out of this. 
> 
> I'll come here from time to time, to answer, well formed thoughtful questions that you might have. Good luck everyone, and enjoy your life. You should sign up for *******.com


 great stuff!

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## fred970

> I have photographs, but* I do not want to publish them for some reasons.*


 Get the hell out of here. Just like every other mad scientist scammer. You have something to sell.

Just put in one line what we have to do or take. Give us some f-ing cliffs. If you can't, no one should listen to what you have to say.

Just look at how our current treatments work: take finasteride and apply minoxidil twice a day. Why can't you do that? *Because you have an agenda*.

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## eldarlmario

Hi, please read Dr Cotsarelis patent(the 2011 one)- it would refute the vast majority of your statements. 

Having always been an 'out-of-the-box' thinker myself, i tried to keep an open mind about what you've said. But it's difficult to do so when you gave the remark that the receptor for 15d pgj2 has not been found, for the well-informed 1 would had known this is not true at all.

So it's either:

1)you are well-aware of the fact that 15d pgj2 is the primary endogenous ligand for the PPAR gamma receptor for stimulating adipogenesis(and to a lesser extent- PPAR Alpha and Beta) as well as the CRTh2 receptor(as proven by Dr Cotsarelis's PGD2 study) butchose feign ignorance for whatever 'secret agenda' that you might have or;

2)you are genuinely unaware of the receptors that 15d pgj2 binds to, which would have stripped all of the rest of what you've claimed to hypothesise of any credibility.

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## Not giving up

> Get the hell out of here. Just like every other mad scientist scammer. You have something to sell.
> 
> Just put in one line what we have to do or take. Give us some f-ing cliffs. If you can't, no one should listen to what you have to say.
> 
> Just look at how our current treatments work: take finasteride and apply minoxidil twice a day. Why can't you do that? *Because you have an agenda*.


 It pains me to say it as we've clashed many-a-time in these threads; but I agree with you, Fred. If he had something real I guess he could just explain it in its simplest form and be done with it. 

No photos, a lot of fancy theoretical scientific terminology that impresses without actually giving much away, I don't think he's a scammer, but something is always off when these posts are presented like this.

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## TJT

Please ban this obvious troll.

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## fred970

> Please ban this obvious troll.


 For a troll, he put a lot of energy into this. No, he wants to gain something from this at a point. So he's more a scammer than a troll.

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## FGF11

*Hi fred970*, I wrote what needs to be done, an exact protocol, and things I've used in my self-experiment. I gave the concentration that I used, the oligo, and how often I did this. There is nothing to gain from this, the only agenda I have, is to take credit for this.  Self-experimentation, is illegal in some countries/states, and JUST because of that I won't publish my pictures. It's also not ethical so journals don't publish results with self-experimentation.

I've given more than "take finasteride, and apply minoxidil twice a week". I've given a complete protocol for it. It's there. It's just that you need to understand it.

There was no way to do it in a simpler way. If it was, I would have done it. I've actually tried to be as simple as possible. you probably haven't/can't completely read what I've written there. Otherwise you wouldn't have said such a thing. And yes, I've hacked it believed it or not and I'm very proud of myself what I've done.

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## fred970

> I've actually tried to be as simple as possible.

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## epipapilla

> For a troll, he put a lot of energy into this. No, he wants to gain something from this at a point. So he's more a scammer than a troll.


 *You, fred970, are far too harsh and far too fastidious!* I guess the balding process turned you into a very cynical person, or is that just an excuse? i.e. is this just your real personality coming out?

Have you ever heard of the saying: "If you can't say something nice, don't say nothing at all?" 

https://www.youtube.com/watch?v=I71cY9Ysy5U

I guess not.

Regardless of whether or not the original poster has ulterior motives, I am absolutely shocked by the way you attack him, and there really is no need for it. I have seen you do this on other threads and hair loss forums too. 

Good day to you! _(or should that be Bad day to you?)_

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## FGF11

*Hi not giving up*, I won't reply to posts [such as this].

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## ElocT9

> There was no way to do it in a simpler way. If it was, I would have done it. I've actually tried to be as simple as possible. you probably haven't/can't completely read what I've written there. Otherwise you wouldn't have said such a thing. And yes, I've hacked it believed it or not and I'm very proud of myself what I've done.


 lol, please sum this up. I read a lot of stupid stuff about hair loss nowadays. If you can not make it simpler, then you probably did not understand the miracle cure yourself.

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## fred970

> *You, fred970, are far too harsh and far too fastidious!* I guess the balding process turned you into a very cynical person, or is that just an excuse? i.e. is this just your real personality coming out?
> 
> Have you ever heard of the saying: "If you can't say something nice, don't say nothing at all?" 
> 
> https://www.youtube.com/watch?v=I71cY9Ysy5U
> 
> I guess not.
> 
> Regardless of whether or not the original poster has ulterior motives, I am absolutely shocked by the way you attack him, and there really is no need for it. I have seen you do this on other threads and hair loss forums too. 
> ...


 Look at my join date, and then look at yours, I've been in this far longer than you've been.

Every other month, some mad scientist comes up with these miracle cures he found in his basement.

----------


## FGF11

*Hi Fred970* I was thinking whether I should do this or not, many times when I did a google search, some of these forums showed up. So I just created an account to share what I did. Now, I did what I needed to do, share my knowledge and findings.  Hope it shows up in some google search of someone. Please remember this, I said many times that this is not a complete treatment (or cure). It needs injections [you can't do that to your whole temples, all the time], It is ridiculously expensive, and it might have side effects when done in bigger scale. Also, if you call being employed in one of the most scientifically advanced places in the world, basement. I have nothing further to add. * This is the last post I have in this forum or any other forum on the web, the only other place I mentioned this was a blog.* Sincerely.

----------


## noisette

> *Hi Fred970* I was thinking whether I should do this or not, many times when I did a google search, some of these forums showed up. So I just created an account to share what I did. Now, I did what I needed to do, share my knowledge and findings.  Hope it shows up in some google search of someone. Please remember this, I said many times that this is not a complete treatment (or cure). It needs injections [you can't do that to your whole temples, all the time], It is ridiculously expensive, and it might have side effects when done in bigger scale. Also, if you call being employed in one of the most scientifically advanced places in the world, basement. I have nothing further to add. * This is the last post I have in this forum or any other forum on the web, the only other place I mentioned this was a blog.* Sincerely.


  On the one hand, I want to thank you for your contribution, but on the other hand, I don't believe you without pics and more proofs... sorry dude  :Wink:

----------


## joachim

i strongly believe that it is possible for a clever scientist with biological talent and understanding to figure out some approaches which were not yet considered by bigger or famous companies or researchers. 
all the things this guy wrote down made sense and sounded really interesting, but now that he was scared away, we will never know. 
if he tried to sell something or scam us, nobody will ever know. 
it was very shortsighted of some members here to critize the guy in that aggressive way. if he were to scam us, we would have found it out soon.
just because he refuses to post pictures at the first moment doesn't mean anything.

so that's it. chance passed by, and we'll continue with histogen, replicel, pilofocus, and the usual waiting games. 

even if one day really a smart guy pops up with real and good research which could shed some new light on the MPB mechanism, he will no chance to be heard. 
people who are not familiar with forums and just try to help by writing some interesting ideas into a forum, will leave very quickly if they only get attacked by all members.

like i said, if it was a troll or scammer who tries to sell something, we would have found out very soon. but until then, there's no need to attack just everyone who comes up with a new idea.

----------


## Hemo

Dude, why don't you just post your protocol (even though you claim to not want people to try it...)?

Also, as detailed as your posts are, no one is going to take it seriously without photos.

----------


## Hubris

> i strongly believe that it is possible for a clever scientist with biological talent and understanding to figure out some approaches which were not yet considered by bigger or famous companies or researchers. 
> all the things this guy wrote down made sense and sounded really interesting, but now that he was scared away, we will never know. 
> if he tried to sell something or scam us, nobody will ever know. 
> it was very shortsighted of some members here to critize the guy in that aggressive way. if he were to scam us, we would have found it out soon.
> just because he refuses to post pictures at the first moment doesn't mean anything.
> 
> so that's it. chance passed by, and we'll continue with histogen, replicel, pilofocus, and the usual waiting games. 
> 
> even if one day really a smart guy pops up with real and good research which could shed some new light on the MPB mechanism, he will no chance to be heard. 
> ...


 Do not worry yourself too much. If you were a scientist and you found a cure or effective treatment to MPB, would you make a few posts on a message board and leave it at that? Anyone familiar with hair loss forums would know that such claims would be met with skepticism - and rightly so.

I do not know if this guy is a fake or not. He posted the exact same thing on a popular hair loss blog a day or two ago. He claims that his protocol utilizes some chemical that only a few people have access to, so we wouldn't be able to experiment with it even if he is telling the truth.

----------


## epipapilla

> Look at my join date, and then look at yours, I've been in this far longer than you've been.
> 
> Every other month, some mad scientist comes up with these miracle cures he found in his basement.


 Because you joined this forum before me or others does not make your posts or points of view any more valid!

Because you have more posts than me or others does also not make your posts any more valid!

Criticism is fine, but you are too far over the top. I can almost feel your misery, cynicism and bitterness through your words of constant pessimism. You certainly are not doing yourself any favours with this mindset.

----------


## xyz123

Honestly - this is fascinating - kind of brilliant - and it makes sense.  

Ultimately, the critical component driving hair loss is the androgen receptor.  And he nicely highlights that the androgen receptor is activated (to subsequently undergo nuclear translocation and impact gene expression) through androgen-dependent and androgen-independent pathways.  This accounts for why DHT is NOT the whole story, but the disease still CENTERS on the androgen receptor.

His story accounts for what is observed from a genetic perspective.  The critical genetic variant on the androgen receptor that leaves us vulnerable to male pattern baldness is carried by 85% of the population (at least among Western Europeans).  If you don't have a copy of this variant, then you won't go bald.  And this accounts for how a male who becomes NW7 at 21 years of age can have a kid that never loses a hair during his whole life (? John Mayer and Orlando Bloom).  He inherited a golden X chromosome from his mother that doesn't carry the AR MPB genetic variant - so no matter what genes he inherits from his father and the remaining genes he inherits from his mother, he'll never go bald - he is protected for life.  This also accounts for how a father who never lost a hair his whole life can give birth to a son who goes NW7 at 19.  The father may have carried a ton of balding genes - but they effectively could never become "active" because he carried the golden X-chromosome - but then his son inherits a regular X-chromosome from his mother and then his balding genes become relevant and destroys the son's life...  :Smile:   This is how balding can skip a generation.

It's only 15% of the population that get this lucky - so for the other 85%, your propensity to develop MPB is influenced by genes from both your mother and your father.  Most of us (well, all of us on this website), carry the genetic variant on the AR that makes us vulnerable to MPB - so we will go bald with time - but the rate and the extent is dependent upon the other MPB disease modifying genes (and there are probably many, many genes involved) that you inherit from both of your parents.  And this is consistent with what we observe - most people end up being a blend of your maternal and paternal genes.  Periodically some people get screwed and inherit all of the MPB disease modifying genes carried by both parents and end up going bald much earlier - and others get lucky and avoid the majority of the MPB disease modifying genes and go bald much later.  

The game changer is the genetic variant on the androgen receptor that can make you immune.

I think he's right - if new drugs are not directly targeting the androgen receptor - they will never be a definitive fix.  Anti-DHT drugs will help - but they don't deal with the cytokines.  And anti-cytokine drugs don't deal with DHT.  And the problem with anti-cytokine drugs is that there are so many different cytokines that can activate the androgen receptor.  So it's not like you can take 1 anti-cytokine drug and a DHT drug and be protected (though that may help a lot).  You'll need to take 20 or more anti-cytokine drugs to be protected from all of the different cytokines (depending upon which pathways are operative in you).

And his comment about anti-DHT drugs being of minimal help when MPB is more advanced also makes sense.  The scalp is full of cytokines that are up-regulating themselves through positive feedback loops - so even if you get rid of DHT, the cytokines will continue to cause AR activation and you'll continue to lose your hair.  So none of the drugs/products under current development are going to be a permanent fix.  Though they will likely be synergistic - if you take multiple drugs that target multiple pathways that converge on the androgen receptor, then you'll get better results.

Assuming he's telling the truth, it is reassuring that inactivating the androgen receptor resulted in re-growth.  I've always worried that, although the stem cells are still there, that fibrosis which developed may prevent complete re-growth.  But maybe not - and that goes along with what has been observed with alopecia areata.

We need a drug that directly targets the androgen receptor.  Not an anti-androgen that prevents androgen binding to the androgen receptor - that's not enough because cytokines will still be able to activate the androgen receptor.  We need a drug that prevents the androgen receptor from being able to translocate into the nucleus.  His anti-sense oligonucleotide would do that (it would prevent the androgen receptor from being translated and hence none would be expressed in the scalp).

Imagine combining the Follicept delivery vehicle (not IGF-1, which was useless - not surprisingly...) with a compound that prevented AR expression in the scalp.  

You probably don't need complete AR suppression in the scalp, though.  The 15% of people that don't carry the AR genetic variant associated with baldness still have functional androgen receptors (unlike people with androgen insensitivity syndrome).  There's something about that variant (and who knows if it's that variant - it could be linked to another genetic variant) that allows androgen receptors to work properly in other aspects of development (allowing you to become a male), but fails to activate the balding process.  But we probably don't need to be that specific - people with androgen insensitivity syndrome have normal hair, so we could just shut down androgen receptors in the scalp.  We are all afraid of side-effects - and there's no way you'd be able to take a drug that shut down androgen receptors systemically.  But a topical that localized to the scalp could work.

It's really interesting - it sounds like they are looking into androgen receptor drugs in prostate cancer.  It's conceivable that - like finasteride - the holy grail for hair loss could evolve from a prostate cancer drug. 

Anyway - I don't know if this guy is telling the truth - re: hair regrowth - but everything he says makes sense.  I'm a physician and a scientist and I think he's made some really interesting inferences.

----------


## NeedHairASAP

NEWSFLASH: He has nothing to sell.

These drugs are already locked down and patented by pharma companies. There is no money for him to make if he didn't share this protocol. He could never monetize it himself.

You can ask for pictures and more information about his protocol, but you can't demand photos or be overly suspicious of him. There is nothing for him to sell, and thus no real reason he MUST post pictures. That doesn't mean we can't ask nicely, but we should not be treating him like he's histogen who is trying to sell us something.

Hopefully he comes back because his insights were interesting, to say the least

Some people on these message boards are unbelievably autistic

----------


## NeedHairASAP

J Allergy Clin Immunol. 2015 Nov 19. pii: S0091-6749(15)01582-1. doi: 10.1016/j.jaci.2015.11.001. [Epub ahead of print]
Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism.
Guttman-Yassky E1, Ungar B2, Noda S3, Suprun M4, Shroff A5, Dutt R5, Khattri S5, Min M5, Mansouri Y5, Zheng X3, Estrada YD5, Singer GK5, Suarez-Farinas M6, Krueger JG3, Lebwohl MG5.
Author information
PMID: 26607705 [PubMed - as supplied by publisher]
Share on FacebookShare on TwitterShare on Google+

----------


## jose1991

What that guy has written is amazing. He is not selling anything. He is just explaining his theory and it makes ****ing sense. Some people here should learn to lisen/read what other people are trying to say before attacking them. He also explains the experiment he did on himself and the drugs he used but, as he says, even if someone rich enough could aford to cover his scalp with it, it's unknown what side effects could it have. The most worrisome is  that if his theory is correct the definitive cure is still pretty far away.

----------


## Westonci

FGF11 please dont go, Fred970 is a dumbass. Just ignore him.

----------


## allTheGoodNamesAreTaken

> Look at my join date, and then look at yours, I've been in this far longer than you've been.
> 
> Every other month, some mad scientist comes up with these miracle cures he found in his basement.


 Some of them find something that works too (Swiss Temples).

----------


## Ulti1

That's nice of you to believe in open science.  The jerk offs over at P*G don't.  I got this feeling they are plotting to monetize something.   Probably RU is my guess.

How they think they are going to compete in price against a Chinese manufacture is beyond me.

----------


## PatientlyWaiting

Well it was an interesting read, and harsh replies. Although like he said, there's not much we can anyway.

----------


## robodoc

> Get the hell out of here. Just like every other mad scientist scammer. You have something to sell.
> 
> Just put in one line what we have to do or take. Give us some f-ing cliffs. If you can't, no one should listen to what you have to say.
> 
> Just look at how our current treatments work: take finasteride and apply minoxidil twice a day. Why can't you do that? *Because you have an agenda*.


 @Fred, what is his agenda?  BS artist with some science background?  If he is BS I am sure his theory is easily refuted. I don't see his statements as a serious agenda.
Clue me in one day.  Something is amiss with his story I will agree.

----------


## robodoc

Photos?  Everyone wants photos.  He postulated a freekin theory and everyone here, like Fred, jumps all over the guy.  I just think if someone is BS we don't the need harsh words and the doubting genius' that know all the frauds because they have been blogging forever.  By someone, his theory was pointed out to be error.  I like intelligent responses and the act of civility is not easy for some miserable people.

----------


## Thinning87

There really was no purpose insulting FGF11. It's not like he ruined anyone's day by opening this interesting thread, so why call him a scammer?

However, FGF11, if you are reading this, you shouldn't get offedned by the things people say on this forum. Most people here, and especially the most active forumers, are in their early 20's.

Hope you come back and continue the conversation! Worst comes to worst, some of us may have an interesting read  :Smile:

----------


## Follisket

Good god, the time and energy some people are willing to expend just to terrify others with theories on how/why a cure isn't likely to be discovered any time soon ... 
How about actually fixing it instead?

----------


## InBeforeTheCure

> His story accounts for what is observed from a genetic perspective.  The critical genetic variant on the androgen receptor that leaves us vulnerable to male pattern baldness is carried by 85% of the population (at least among Western Europeans).  If you don't have a copy of this variant, then you won't go bald.  And this accounts for how a male who becomes NW7 at 21 years of age can have a kid that never loses a hair during his whole life (? John Mayer and Orlando Bloom).  He inherited a golden X chromosome from his mother that doesn't carry the AR MPB genetic variant - so no matter what genes he inherits from his father and the remaining genes he inherits from his mother, he'll never go bald - he is protected for life.  This also accounts for how a father who never lost a hair his whole life can give birth to a son who goes NW7 at 19.  The father may have carried a ton of balding genes - but they effectively could never become "active" because he carried the golden X-chromosome - but then his son inherits a regular X-chromosome from his mother and then his balding genes become relevant and destroys the son's life...   This is how balding can skip a generation.
> 
> It's only 15% of the population that get this lucky - so for the other 85%, your propensity to develop MPB is influenced by genes from both your mother and your father.  Most of us (well, all of us on this website), carry the genetic variant on the AR that makes us vulnerable to MPB - so we will go bald with time - but the rate and the extent is dependent upon the other MPB disease modifying genes (and there are probably many, many genes involved) that you inherit from both of your parents.  And this is consistent with what we observe - most people end up being a blend of your maternal and paternal genes.  Periodically some people get screwed and inherit all of the MPB disease modifying genes carried by both parents and end up going bald much earlier - and others get lucky and avoid the majority of the MPB disease modifying genes and go bald much later.


 Which variant in the androgen receptor gene are you referring to exactly? Can you link me to the paper where the 85% figure comes from?

----------


## Dench57

I've no idea why somebody who has clearly put a lot of time and effort into figuring out this disease, then sharing his theories with everyone, has been met with such nasty replies. Good going guys.

The more intelligent, diligent, BALDING people from a scientific background we have working on this the better. You can be damn sure nobody else cares about us.

----------


## xyz123

Original paper is below - it's the Stu1 restriction site.  It may not be the functional culprit (it may be tagged to a functional culprit that's yet to be elucidated - and hence the numbers don't work out to exactly 100%).  But whatever this tags - it is the gatekeeper for MPB.  If you don't have it, you keep your hair.  That said - it's necessary, but not sufficient.  Even 75% of non-bald guys have it - that's where the MPB disease modifying genes start to play a role.  

We need a drug that down-regulates expression of the androgen receptor in the scalp.

http://www.nature.com/jid/journal/v1.../5601004a.html

----------


## Follisket

Well, he's basically saying that, according to his theory, none of the treatments in development currently would really work, and the one thing he _supposedly has_ figured out is too hard and too expensive to do, and couldn't possibly be out within the next 10 years. Some cure/treatment that is.

And people actually get excited over the prospect of finally having a full head of hair at the age of 70? Jeez, no wonder baldies are screwed.

----------


## xyz123

No - that's not it at all.

His theory - which I think may actually be correct - accounts for the limited efficacy of current treatments (and that's totally accurate - current treatments have incredibly limited efficacy).

His theory is not that complicated.  Yes - there are a million pathways in MPB - but all converge on the androgen receptor.  That's why - if you take a drug that affects one pathway - its overall impact is limited because there are multiple other pathways that continue to stimulate the androgen receptor.  I think everyone thought that MPB was due to a linear cascade of events - but it's probably not.  It's multiple parallel pathways that converge on the androgen receptor.

His insight was driven by work in prostate cancer ,which has recognized that the androgen receptor can be activated by - not just DHT - but multiple other pro-inflammatory factors.

A typical diagram: http://www.carcinogenesis.com/viewim...0_83937_f2.jpg




Honestly - this explains so much.  It's why things that create increased scalp inflammation in vulnerable people accelerate baldness - whereas there's no effect in non-vulnerable people.  It's why harsh shampoos that contain sodium lauryl sulfate can accelerate baldness in vulnerable individuals (by creating scalp inflammation) - but have no effect on non-vulnerable people.  (which led people to say that baldness being caused by harsh shampoos is a myth - which is partially true - but it can definitely accelerate the process).  

And this shouldn't be viewed as discouraging.  Yes - none of the current treatments will be a definitive cure (as expected) - but if someone can develop a drug that down-regulates the androgen receptor in the scalp - which should not be that hard (the hardest part of this stuff is finding the critical target; which in hindsight was probably right in front of us all along) - then it's conceivable a drug could be developed fairly quickly.

I think this is really encouraging.  We're borrowing from discoveries and breakthroughs from another field to break new ground in our area.  This happens a lot in medicine - and is often how major breakthroughs occur.  Keep the faith  :Smile:

----------


## InBeforeTheCure

> Original paper is below - it's the Stu1 restriction site.  It may not be the functional culprit (it may be tagged to a functional culprit that's yet to be elucidated - and hence the numbers don't work out to exactly 100%).  But whatever this tags - it is the gatekeeper for MPB.  If you don't have it, you keep your hair.  That said - it's necessary, but not sufficient.  Even 75% of non-bald guys have it - that's where the MPB disease modifying genes start to play a role.  
> 
> We need a drug that down-regulates expression of the androgen receptor in the scalp.
> 
> http://www.nature.com/jid/journal/v1.../5601004a.html


 Thanks. As far as I can tell, that's the marker also known as rs6152.

There's also this:




> Abstract:
> 
> Androgenetic alopecia (AGA) is a common heritable polygenic disorder whose genetics is not fully understood, even though it seems to be X-linked. We carried out an epidemiological survey for AGA on 9,000 people from 8 isolated villages of a secluded region of Sardinia (Ogliastra), and identified a large cohort of affected individuals. We genotyped 200 cases and 200 controls (mean kinship 0.001) with the 500k chip array and conducted casecontrol association analysis on the X chromosome. We identified Xq11-q12 as strongly associated with AGA. In particular, we found that rs1352015 located 8 kb from the EDA2R gene showed the best result (P=7.77e−7). This region also contains the AR gene, hence we tested both genes in 492 cases and 492 controls. *We found that the non-synonymous SNP rs1385699 on EDA2R gave the best result (P=3.9e−19) whereas rs6152 on the AR gene is less significant (P=4.17e−12). Further statistical analysis carried out by conditioning each gene to the presence of the other showed that the association with EDA2R is independent while the association with AR seems to be the result of linkage disequilibrium.* These results give insight into the pathways involved in AGA etiology.


 


> Our study shows that AR and EDA2R are significantly associated with AGA. However, there is some LD between the two most associated markers for each gene (rs6152, rs1385699: D′=0.74, r2=0.43). To test if they are independently associated, we conditioned the analysis of each gene to the other one. We used the UNPHASED software (Dudbridge, 2003), which permits the association of a marker to be conditioned to the presence of another marker. The analysis of rs1385699 conditioned to the presence of rs6152 gave a very significant P-value of 6.136e−9, whereas when we conditioned the analysis of rs6152 to the presence of rs1385699 the P-value was 0.04. Again, rs1385699 conditioned to the presence of rs12558842 gave a very significant result (P-value 0.007), whereas rs12558842 conditioned to the presence of the EDA2R variant did not give a significant result (P-value 0.06). These results show that in our population, the EDA2R gene variation causes susceptibility to AGA. The conditioned analysis suggests that markers on the AR gene could be associated because of LD. However, we cannot exclude that other variants in LD with both genes (that is, regulatory elements of either or both genes) could be associated with AGA. Moreover, the functional importance of AR has already been proven by many means, and its involvement in this pathology cannot be excluded. Further functional and genetic studies are needed to clarify the role of these two genes and their possible interactions in the etiology of AGA.


 


> Two receptors for EDA were found that are specific for the two isoforms EDA-A1 and EDA-A2: EDAR and EDA2R, respectively. EDA-A1 and its receptor EDAR are capable of activating the NF-κB pathway and are implicated in hair growth (Botchkarev and Fessing, 2005). EDA2R is capable of activating the NF-κB pathway and also through TRAF3,6, JNK (c-Jun N-terminal kinase) (Sinha et al., 2002), which activates c-Jun. Mutations in EDA and EDAR give rise to ectodermal dysplasia, a clinical syndrome characterized by loss of hair, sweat glands, and teeth, whereas mutations in EDA2R do not (Monreal et al., 1999; Naito et al., 2002; Newton et al., 2004). Recently, a preliminary report suggested that EDAR may influence hair thickness in Asians (A. Fujimoto, R. Kimura, J. Ohashi, U. Samakkarn, W. Settheetham-Ishida, T. Ishida, Y. Morishita, T. Furusawa, M. Nakazawa, R. Ohtsuka, R. Yuliwulandari, L. Batubara, M.S. Mustofa, K. Tokunaga, A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness, ASHJ Meeting 2007). EDA2R could influence the onset of AGA through the activation of the NF-κB pathway or by c-Jun, which has been shown to be critical for AR transactivation (Bubulya et al., 1996). Moreover, in adult mice, EDA2R is also expressed in the hair bulb and in differentiating hair matrix (Botchkarev and Fessing, 2005). Looking at the human expression data from the UniGene database (http://www.ncbi.nlm.nih.gov/sites/entrez), we noticed that it is expressed during embryonic life and, especially, in the first weeks after birth. Expression then seems to be absent until the 17th year of age, when it recurs in different tissues, including skin. This expression pattern fits very well with the course of AGA, with its onset around puberty.


 Source: http://www.nature.com/jid/journal/v1...id200860a.html

I actually have

rs6152 = A (the non-risk allele, present in only 1 of the 54 young balding men in the paper you cited)

rs1385699 = T (the risk allele on the EDA2R gene, associated with baldness)

----------


## trunks

First of all I want to really thank you FGF11 for your experiment. However some photos as a proof would be gently welcomed (I belive in this theory even without a proof though)

I am posting some studies connected to silencing mutated AR. Probably there is a way to create topical solution with minimal side effects and if your claims are true - that would be a next generation ULTIMATE CURE. 

So please FGF11 show us the proof, after that we should try to make this gene therapy happen.

Silencing the androgen receptor: New skills for antiandrogen oligonucleotide skin and hair therapy




> Antiandrogen therapeutic oligonucleotides  targeting  the  downregulation  of  the  ARexpression is advantageous because both will be possible to eliminate the only way for androgens to act and simultaneously *this strategy allows the medication to be topically administrated*.


 Control of androgen receptor expression in human keratinocytes and in a reconstituted human epidermis model with selective antisense oligonucleotides




> Association of locally increased androgen activity and skin disorders is obvious in acne and androgenetic alopecia in males. In addition, testosterone was unexpectedly found to perturb the epidermal barrier. Blockade of androgen action via androgen receptor (AR) antagonism accelerates wound healing in aged individuals. *Androgen activity on skin can classically be inhibited by systemic administration of compounds, which have strong affinity for AR and antagonize androgen binding to AR molecules. In this study we applied a new technology to realize the same purpose: We tested the activity of antisense oligonucleotides against the AR* in primary human foreskin keratinocytes, human non-foreskin keratinocytes from young (30 y) and older (60 y) female donors, and reconstituted human epidermis (SkinEthic model). Reconstituted human epidermis is similar to in vivo human epidermis and features a functional permeability barrier. To transfer the antisense oligonucleotides into human keratinocytes an optimum liposome-mediated transfection system with Poly-L-ornithine (12 μg/ml) over 4 h was used. The transfection efficiency was assessed using FITC-labeled (ACTG)5 random oligonucleotides, which were localized in cytoplasmic structures of the keratinocytes. AR expression on the protein level was investigated by Western blotting. Transient transfection of foreskin keratinocytes with phosphorothioate antisense oligonucleotides (PTO) revealed a reduction of AR expression (≈25%) compared to native keratinocytes after 14 h recovery time. The AR knock down in epidermal keratinocytes of the compared women was stronger in the older, more differentiated keratinocytes. After 24 h, AR expression level have returned back to the level of non-transfected cells. The effect could be reestablished by repetition of transfection. PTO and 2?O-methylribosyl (MRO) antisense oligonucleotides decreased AR expression at levels varying between 46% and 70% in the air-lifted reconstituted human epidermis after 18 h recovery time. *The successful inhibition of AR expression in human keratinocytes and reconstituted human epidermis is the first step to develop topically efficient compounds with oligonucleotides*

----------


## Swooping

Thanks for your effort.

Inactivation/silencing of AR will most definitely not reverse miniaturization though. I'm extremely sure of this so I automatically put your story into question. 

Proof is what I want to see.

----------


## FGF11

> First of all I want to really thank you FGF11 for your experiment. However some photos as a proof would be gently welcomed (I belive in this theory even without a proof though)
> 
> I am posting some studies connected to silencing mutated AR. Probably there is a way to create topical solution with minimal side effects and if your claims are true - that would be a next generation ULTIMATE CURE. 
> 
> So please FGF11 show us the proof, after that we should try to make this gene therapy happen.
> 
> Silencing the androgen receptor: New skills for antiandrogen oligonucleotide skin and hair therapy
> 
> 
> ...


 


To make more sense out of antisense oligos:

#1 Most of topical solutions act through HFs, what it means is that many of the topical solutions that deliver oligonucleotides pass epithelium into dermis, through the hair shaft (maybe). They concentrate there. Now, most of the studies done in hairless mice with oligo topical solutions (for silencing other genes) do not work (usual topical solutions I mean). However, the same studies work in mice with HFs. Therefore, if the area, is not covered with visible large HFs, the efficiency of Oligo should be extremely low. 

#2) The best scientific experiment would be injection (PLEASE DO NOT TRY THIS). But if I were to suggest something, I would say a microneedle semi-auto tattoo gun (they are dermal guns), would probably be the best away to efficiently and vastly introduce oligo every three - four days, fast for a large area. However, it will be inefficient, and more expensive.

3) You should remember, maybe, the physical disruptions, introduced while adding the oligos, were MAYBE HELPING in disrupting the fibrosis (whether it is there or not). Injecting intradermally, makes a gap between dermis and epithelia, for about 30 minutes, every time. By pushing epithelia upward, this may (theoretically) be the reason why the topical would not work.

4) Yes, there are a couple of patents regarding silencing AR that may or may not (I'm not a lawyer) be able to lock the technology. None of them, however, to my understanding, have really tried this, even for ONCE. They did only file the patent, for when such a day would come. Even there are one or two studies trying to silence AR. Those studies are not good studies. 

5) This is NOT going to be the ultimate treatment (Please don't use the word cure referring to hair loss - it's an aesthetic condition). This however, will be, extremely more effective treatment with oligo's, and it may actually be very SAFE.

6) Triple repeats in AR do not only correlate with AGA but they also correlate with rheumatoid arthritis (RT). Pointing toward a role for AR in AGA and RT. 

I appreciate when you share intelligent comments. Please contribute intelligently, otherwise, don't.

----------


## uzumakinaruto

Hi sorry for the noob question- does that mean, if im reading it right- that ablating the AR receptor in the hair follicles on the hairless scalp will resolve hair loss and regrow hair?

----------


## xyz123

> Thanks for your effort.
> 
> Inactivation/silencing of AR will most definitely not reverse miniaturization though. I'm extremely sure of this so I automatically put your story into question. 
> 
> Proof is what I want to see.


 Agree - proof is critical.

But how can you be certain that silencing of AR won't reverse miniaturization?  As highlighted - this is not the same as complete androgen deprivation (like what happens with trans-genders).  As we know, trans-genders with pre-existing baldness do not regrow most of their - but as he indicated, this may be secondary to continued activation of the AR through non-androgen dependent pathways.

I don't think we have any evidence to indicate that silencing of AR will not regrow hair - has this ever been done/tried before?  If his theory is correct, the AR is the final common pathway - everything converges on the AR to trigger and maintain baldness.  If you reduce/eliminate AR, follicles should be released and able to grow again - regardless of how much PGD2, TGF-beta, etc. that you have floating around your scalp.

----------


## xyz123

> Thanks. As far as I can tell, that's the marker also known as rs6152.
> 
> There's also this:
> 
> 
> 
> 
> 
> 
> ...


 
Interesting.  Yeah - I guess we don't know what those variants are tagging - but it definitely involves the AR.  The real culprit is probably a non-coding SNP that impacts AR levels.  People who don't go bald probably have much lower AR levels in their follicles - and hence no matter how much DHT is circulating, it's not sufficient to trigger the AR positive feedback loop that triggers balding - there's just not enough AR to reach the necessary threshold.  Interesting about EDA2R - and again - it looks like it interacts with AR - ? also involved in its upregulation or increased activity levels. 

It all still fits with his theory - reduce AR in the scalp and you will solve balding.  Very encouraging that it looks like other groups have already worked on developing oligonucleotides to reduce its expression - that's exactly what OP was doing - it definitely seems feasible.

----------


## xyz123

> To make more sense out of antisense oligos:
> 
> #1 Most of topical solutions act through HFs, what it means is that many of the topical solutions that deliver oligonucleotides pass epithelium into dermis, through the hair shaft (maybe). They concentrate there. Now, most of the studies done in hairless mice with oligo topical solutions (for silencing other genes) do not work (usual topical solutions I mean). However, the same studies work in mice with HFs. Therefore, if the area, is not covered with visible large HFs, the efficiency of Oligo should be extremely low. 
> 
> #2) The best scientific experiment would be injection (PLEASE DO NOT TRY THIS). But if I were to suggest something, I would say a microneedle semi-auto tattoo gun (they are dermal guns), would probably be the best away to efficiently and vastly introduce oligo every three - four days, fast for a large area. However, it will be inefficient, and more expensive.
> 
> 3) You should remember, maybe, the physical disruptions, introduced while adding the oligos, were MAYBE HELPING in disrupting the fibrosis (whether it is there or not). Injecting intradermally, makes a gap between dermis and epithelia, for about 30 minutes, every time. By pushing epithelia upward, this may (theoretically) be the reason why the topical would not work.
> 
> 4) Yes, there are a couple of patents regarding silencing AR that may or may not (I'm not a lawyer) be able to lock the technology. None of them, however, to my understanding, have really tried this, even for ONCE. They did only file the patent, for when such a day would come. Even there are one or two studies trying to silence AR. Those studies are not good studies. 
> ...


 
Thanks so much for your contributions FGF11 - they are really intriguing.

Daily injections over your entire scalp is obviously not ideal - but it may not be necessary.  Earlier this year a company called Prometheon Pharma (http://www.prometheonpharma.com/) was touting a trans-dermal delivery vehicle for large molecules (as big as insulin) and tried to use it with IGF-1 to regrow hair.  Not surprisingly, it failed to regrow hair because IGF-1 is insufficient to combat AGA.  

But their trans-dermal delivery vehicle could be ideal for oligonucleotides - effectively converting your therapy into a topical cream that could be applied daily.

Thoughts?  Thanks again for your insights.

----------


## Westonci

*Summary of FGF11's Findings*

You need to de-activate the androgen recepetor (AR), because it is activated by both Hormones (DHT) and cytokines. Thats why finasteride is not a total solution, it acts on the dht side of the equation but not the cytokine problem.

Thanks so much FGF11

----------


## Swooping

> Agree - proof is critical.
> 
> But how can you be certain that silencing of AR won't reverse miniaturization?  As highlighted - this is not the same as complete androgen deprivation (like what happens with trans-genders).  As we know, trans-genders with pre-existing baldness do not regrow most of their - but as he indicated, this may be secondary to continued activation of the AR through non-androgen dependent pathways.
> 
> I don't think we have any evidence to indicate that silencing of AR will not regrow hair - has this ever been done/tried before?  If his theory is correct, the AR is the final common pathway - everything converges on the AR to trigger and maintain baldness.  If you reduce/eliminate AR, follicles should be released and able to grow again - regardless of how much PGD2, TGF-beta, etc. that you have floating around your scalp.


 Why you think that secondary activation of AR is that important through non-androgen dependent pathways? If that were to be true then why do castrated people never develop AGA if they are
castrated before puberty? Secondly why does their balding stop when they are castrated when suffering from AGA? If secondary activation through  non-androgen dependent pathways was a problem it would be expected that AR would still cause problems in these people,  but it doesn’t. Their balding stops.  Injecting these castrated people with testosterone causes their hair to fall out again. This has been all shown ages ago by Hamilton. 

I think Cotsarelis puts this well; 




> We know a lot about AGA from studies a long time ago, in the ’50s, by Dr. James Hamilton. He was the first one to coin the term androgenetic alopecia. He noticed that men who had been castrated before puberty never went bald, and realized that baldness was androgen-dependent. He did some experiments where he gave men who had been castrated testosterone; the ones who had a family history of baldness started to go bald, so that was how he identified the genetic component. He originally called it androchronogenetic alopecia because you needed androgens, time, and genetics. We’ve known it’s androgen-dependent since then.


 So, yes AGA is androgen dependent. Remove androgens and AGA ceases to exist pretty much (the same could be said for AR).  

If you remove androgens or AR then all downstream factors that were harmful  before become irrelevant. After all balding stops when you remove androgens, so apparently these downstream factors that were harmful before suddenly are not damaging anymore in terms of progression of AGA.  

So indeed that begs the question; why doesn’t the hair follicle revert to the original state in that case? Many people have problems with this fact. But here is exactly where the consensus of many researchers comes into place.  It’s simply damage over time that leads to an altered cell state. I don’t know why many people seem to neglect these papers/evidence. It’s way more accepted for instance than the PGD2 hypothesis. Way more logical too, at least to me. 

Take a piece of plastic and heat. Now the piece of plastic is the hair follicle and the heat in this case  is the damage (Androgens and AR upstream signals known). Eventually the plastic will start to melt and adopts a new form. Now your remove the heat but does the plastic re-shape itself to it’s original form? I don’t think so. 

If you are interested more into this literature I suggest you to start reading about this. Here are some to start; 

http://www.ncbi.nlm.nih.gov/pubmed/17989730
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/
http://www.ncbi.nlm.nih.gov/pubmed/18702626
http://www.ncbi.nlm.nih.gov/pubmed/21967250
http://www.ncbi.nlm.nih.gov/pubmed/25778683
http://journals.plos.org/plosone/art...l.pone.0031052


I would just like to call AR activation due to androgens “stress”. This stress sets in motion extremely major important pathways that alter these cells. These are not factors like PGD2, TGF-b, DKK1. Nah,  it gets more way more important than that and these studies clearly show these pathways. All the microRNA studies also reflect upon these pathways. 




> “a process that is thought to reflect irreversible cell growth arrest in the progression of AGA.”


 Now one might ask the question; But hey we remove all androgens so these major important pathways don’t get activated anymore, so why the hell doesn’t my hair follicle reverse to it’s original state?  Well wouldn’t that be inefficient? It's just how it works. 

If we look for example on P53 only just as a pure example (don't look at the tumor suppression although this is also a function of P53); 



Get it? P53 for instance (which is over expressed in scalp as you can see in the study) can decide that damage is to big and it can cause apoptosis or permanent cell cycle arrest and create a very tough "lock" if that makes sense to you. Now it might not be P53 which is causing this but you get the point. It's perhaps some sort of efficient lock, a lock that got activated due to the stress on the cells. Or apoptosis or a combination of both. I'm not saying that P53 is implicated it just acts as an example, but evidence has been shown in papers that it is probably implicated. Go have a read for fun on the function of P53 overall. 

Anyway there could be said much more about this. Everything falls into place and makes sense if you read those studies and understand what these pathways do and why they act like that. I think clearly the "broad" picture is becoming clear. 

Anyway didn't mean to hijack this topic. Answers your question why full AR silencing won't act as a cure or reverse hair miniaturization in to great extent. Sure some people will have some regrowth. But guess what some people also have some regrowth with finasteride/dutasteride/RU58841. In this case I guess (some) damage of the cells was still repairable. But acting as a cure? Nah, doubt it very much. Highly unlikely. 


*Burden of proof is on OP anyway,* cause he is the one making very bold claims.

----------


## fred970

Do you all always go take a piss when Spencer says: "Take everything you read on the forums with a grain of salt"?

No way I'm reading all that crap, some of us have lives. I will trust real world scientists over forum mad scientists any day.

Have fun making another of these 100 pages thread who will be buried and forgotten in a few years. Joining the hall of fame made of threads like these:

https://www.baldtruthtalk.com/threads/3759-Trx2

https://www.baldtruthtalk.com/thread...in-alternative

https://www.baldtruthtalk.com/thread...ommunity-Trial

https://www.baldtruthtalk.com/thread...own-experience

https://www.baldtruthtalk.com/thread...2%92Or%C3%A9al

So much energy spent and what did we gain from these threads? Jack.

----------


## Chemical

> If you are interested more into this literature I suggest you to start reading about this. Here are some to start; 
> 
> http://www.ncbi.nlm.nih.gov/pubmed/17989730
> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/
> http://www.ncbi.nlm.nih.gov/pubmed/18702626
> http://www.ncbi.nlm.nih.gov/pubmed/21967250
> http://www.ncbi.nlm.nih.gov/pubmed/25778683
> http://journals.plos.org/plosone/art...l.pone.0031052
> 
> ...


 I'd like to expand on what swooping just mentioned, since I've taken the time to actually read those studies relating to P53, p21, p16 what exactly their roles are in tumor suppression.

It is a known fact Androgens cause DNA damage, this is in part due to evolutionary adaptations and stupid mutations. How and why is the crucial topic of interest which people love avoiding.

*This study* shows that Cyclin d1, a cell cycle progression protein is necessary to mediate DHT dependent DNA damage. Testosterone mediates most of its androgenic effects via autorine/paracrine conversion to DHT which binds to nuclear or neighbouring cell surface AR receptors. 

Cells must proliferate and regenerate continuously, therefore it is inevitable that they will accumulate DNA damage over time, and moreso when you add in reactive oxygen species. Androgens increase IGF-R, there are many studies outlining this, but IGF-1 is a known cancer promoting agent. IGF-1 causes enhanced cell hypertrophy and proliferation, which translates to more Cyclin d1 => more DNA damage. This is why the body has developed counter measures to protect against this. The tumor suppressor family of p53/p21/p16 all exert their effects by reducing proliferation of cells and achieving premature senescence. If the cells continue to proliferate with DNA damage, they will end up becoming cancerous. Our ancestors that developed these feedback loops survived, explaining why we have them in the first place. 

What do these p-family genes do? 

p16:




> p16 is a cyclin-dependent kinase (CDK) inhibitor that *slows down the cell cycle by prohibiting progression* from G1 phase to S phase. Normally, CDK4/6 binds cyclin D and forms an active protein complex that phosphorylates retinoblastoma protein (pRB). Once phosphorylated, pRB disassociates from the transcription factor E2F1, liberating E2F1 from its cytoplasm bound state allowing it to enter the nucleus. Once in the nucleus, E2F1 promotes the transcription of target genes that are essential for transition from G1 to S phase.[9][10]
> 
> *p16 acts as a tumor suppressor by binding to CDK4/6 and preventing its interaction with cyclin D.* This interaction ultimately inhibits the downstream activities of transcription factors, such as E2F1, and arrests cell proliferation.[10] This pathway connects the processes of tumor oncogenesis and senescence, fixing them on opposite ends of a spectrum. On one end, the hypermethylation, mutation, or deletion of p16 leads to downregulation of the gene and can lead to cancer through the dysregulation of cell cycle progression. Conversely, activation of p16 through the ROS pathway, DNA damage, or senescence leads to the buildup of p16 in tissues and is implicated in aging of cells.[9]


 So it inhibits the proliferation of cells and promotes cellular senecense (cells have a certain number of replication cycles determined by telomerase - which is why we have stem cells, and even they can achieve senescence which is the secret to anti-aging but thats another post)

p21:




> p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, and thus functions as a regulator of cell cycle progression at G1 and S phase.[5] In addition to growth arrest, p21 can mediate cellular senescence. One of the ways it was discovered was as a senescent cell-derived inhibitor.


 once again similar to p16 but has additional effects on DNA damage repair.

p53:




> p53 has many mechanisms of anticancer function and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works through several mechanisms:
> 
> It can activate DNA repair proteins when DNA has sustained damage. Thus, it may be an important factor in aging.[30]
> It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle).
> It can initiate apoptosis (i.e., programmed cell death) if DNA damage proves to be irreparable.


 p53 has  a far more diverse role. Not only does p53 inhibit cell cycle progression, it attempts to repair the damage. A good thing right? it would be if thats all did. P53 is good for the prostate because it tries to prevents DHT driven prostate cancer via WNT. It inhibits the canonical WNT signalling pathway (aberrant wnt signalling leads to cancer ), however, stupidly, the prostate is incredibly similar to the scalp - I've covered this in more detail in my other thread. 

p53 induces DKK1 to inhibit WNT signalling and WNT binding to LRP6:




> p53 is a tumor suppressor and loss of p53 function accelerates mammary tumorigenesis by Wnt. In this study, we found that Dkk-1 is induced by wild-type p53 but not mutant p53(R249S). In addition, *DNA damage upregulates Dkk-1 in cell lines that harbor an endogenous wild-type p53 gene but not in cell lines that are p53-null or harbor an endogenous mutant p53 gene.* We also found a potential p53 responsive element located approximately 2100 nucleotides upstream of the Dkk-1 transcription start site and we show that p53 binds specifically to this element both in vitro and in vivo. Furthermore, we have established several cell lines derived from H1299 lung carcinoma and U118 glioma cells that inducibly express Dkk-1 under a tetracycline-regulated promoter. We found that Dkk-1 has no effect on proliferation of cells that are not transformed by Wnt. *Taken together, these results suggest that Dkk-1 may mediate p53 tumor suppression by antagonizing the Wnt signaling pathway.*


 *p53 Activates MicroRNA-34 to Inhibit Wnt Signaling*

now why the f*** would you inhibit WNTs in hair follicles? We're not going to frickin die from excessive hair growth. I still dont understand why the body has these mechanisms, its just blindly evolving using whatever works in the short term, but that's the beauty of evolution i guess.

so to conclude, yes androgens cause senescence and DNA damage, but they work through pathways that can be targeted/exploited with different and feasible strategies than just silencing the very broad Androgen receptor. 

Personally I think the androgen receptor - if inhibited, can allow other treatments to work far more effectively. FGF11s research has promise but I'd like some more supporting evidence both in terms of theory and practical use.

----------


## just2hairs

> Do you all always go take a piss when Spencer says: "Take everything you read on the forums with a grain of salt"?
> 
> No way I'm reading all that crap, some of us have lives. I will trust real world scientists over forum mad scientists any day.
> 
> Have fun making another of these 100 pages thread who will be buried and forgotten in a few years. Joining the hall of fame made of threads like these:
> 
> https://www.baldtruthtalk.com/threads/3759-Trx2
> 
> https://www.baldtruthtalk.com/thread...in-alternative
> ...


 So why are you here?  Just to piss on people?

----------


## FGF11

> Why you think that secondary activation of AR is that important through non-androgen dependent pathways? If that were to be true then why do castrated people never develop AGA if they are
> castrated before puberty? Secondly why does their balding stop when they are castrated when suffering from AGA? If secondary activation through  non-androgen dependent pathways was a problem it would be expected that AR would still cause problems in these people,  but it doesn’t. Their balding stops.  Injecting these castrated people with testosterone causes their hair to fall out again. This has been all shown ages ago by Hamilton. 
> 
> I think Cotsarelis puts this well; 
> 
> 
> 
> So, yes AGA is androgen dependent. Remove androgens and AGA ceases to exist pretty much (the same could be said for AR).  
> 
> ...


 *Swooping,* 

I know about stress and senescence. I've read those papers.

I get them. *I can make something up here easily*, I don't want to cherry pick or skew the facts when coming to theories.  It's easy to pretend you talk science, but no studies so far have been done on what I wrote. The only study so far is what I've done, with my very limited resources. It will be interesting to investigate Nuclear translocation of AR of HFs, for example, in Castrated-Mice in presence and absence of selective cytokine signals to see its effect on HF cycle. Or to see the effect of cytokines, in HFs, on migration and secretion of Growth Factors. Or analyze if cytokine treatment of transplanted Human HF, will cause AR nuclear localization in the back of SCID mice or not. So many studies that can be done.

Or I can say for example:

1) Yes, they don't go bald (Castrated Males) Why? 

Since androgen as an initial signal is needed to get cells activated to produce cytokines in the first place. 

When androgen is totally absent cytokines, are not made in the HFs, and the eventual add up of cytokines therefore never happen. 

Now, imagine, when cytokines (or some other factors) levels are low, the activation of AR is majorly androgen dependent, while they start to add up, it become androgen independent, lessening and lessening the need for androgen-dependent signalling. 

2) It's not only about cytokines, I'm talking the big picture here. AR, will lock other transcription factors such as FOXa2 and Beta-catenin, to have their normal function in the nucleus. So, It's knockdown will cause secretion a set of growth factors, such as WNTs, and activating epithelial stem cells in a co-ordinate manner to divide. 

3) Or I can stress is reversible (my M.Sc. was on stress signals and ERAD) and through some papers for it (but you seem to have a biological background so you know what I say)

The truth though is that we don't know.

----------


## FGF11

Also I don't remember using the word cure. I have a philosophical problem with that word.

So just to clear things up again, please don't say that I have said I have the cure. I've mentioned many times that I don't. So many times, that even, someone thought, I said it's ten years away. 

I see some intelligent comments showing up. That's great people. Thanks.

----------


## xyz123

To Swooping and Chemical: thanks guys - you both seem to know the science cold.  And again - FGF11 - appreciate your insights.  This is a pretty high level thread.  You could probably stitch enough together to make for a fancy review article in a journal (not that we care about that  :Smile:  ).

----------


## fred970

> So why are you here?  Just to piss on people?


 To warn them not to waste their time reading this, obviously.

This is going to lead nowhere. I've been on these forums for 7 years, this kind of thread never leads to anything.

----------


## jamesst11

> To warn them not to waste their time reading this, obviously.
> 
> This is going to lead nowhere. I've been on these forums for 7 years, this kind of thread never leads to anything.


 this is true, however... Very well researched and put together, but it is no answer and there is no reasonable protocol for this.

----------


## just2hairs

> To warn them not to waste their time reading this, obviously.
> 
> This is going to lead nowhere. I've been on these forums for 7 years, this kind of thread never leads to anything.


 Even if this leads to nowhere, i appreciate people sharing their knowledge and research.  I rather read FGF11's findings than your negative rants...which REALLY leads to nowhere.

----------


## FGF11

Hi fred970 

Well, instead of wasting your time reading my stuff here. I suggest you watch this movie, it's based on a true story  :Smile: 

https://www.youtube.com/watch?v=tZV_bMgB-zA

never underestimate the power of a very motivated person

And always remember this:

"be the change you want to see in the world"

Hope you have a great day

----------


## bigentries

> Even if this leads to nowhere, i appreciate people sharing their knowledge and research.  I rather read FGF11's findings than your negative rants...which REALLY leads to nowhere.


 You probably don't know Fred's history

He also shared his "knowledge and research", rallied against "negative rants", had a bunch of supporters from the start, specially in "alternative" forums he was sort of a celebrity

Then he really started to lose his hair

Since then he did a complete rework of his personality and became an skeptic, which got him banned from the forum he was so loved.

I admire Fred because unlike many "gurus" and scam pushers that exists in these place, at least he admitted he did wrong, spread a lot of misinformation, and is trying to make up for it. Some just disappear or hop into the next scam

----------


## NeedHairASAP

> Hi fred970 
> 
> Well, instead of wasting your time reading my stuff here. I suggest you watch this movie, it's based on a true story 
> 
> https://www.youtube.com/watch?v=tZV_bMgB-zA
> 
> never underestimate the power of a very motivated person
> 
> And always remember this:
> ...


 What is so ironic is that Fred is accusing you of being a troll, whilst he himself is the biggest troll in this entire thread.

----------


## FGF11

I figured out a novel way to do my experiments in a much larger scale and for a longer amount of time, this is for me a very important time. So as of now I have decided to go ahead with this. (I may or may not however do this, also I may or may not post my results here), If I decide to go with it (after I totally get sure if it's safe), it probably will six or eight months, or even more till I get sure it works. Well, what I can say it's my hobby. Everyone has hobby, right? Anyways, here I wrote a last "scientific" reply further supporting it might be possible to reverse HF miniaturization. This time, I'm "REALLY" off this tread though. I appreciate those few critical responses I've got, from xyz123, chemical, swooping and everyone else for appreciating me writing my theory here. Good Luck.

Current drug treatments for MPP, Finasteride and Minoxidil, usually have only marginal effect on hair density. This is, despite the fact that, the bald region of scalp in MPB patients still retains the capacity for full regeneration of its hair follicles (1). In an experiment done by Krajcik et al, authors showed that not only hair follicles (HFs) from bald scalp can grow as fast as HFs from hairy scalp when transplanted onto the back skin of SCID mice, but also strikingly, they even produce a thicker shaft (2). Reversal of MPB has also been reported in patients on immune-related drugs (3). These data are promising as they provide the interested researcher with the much needed confidence that transformation of vellus hairs from bald region of scalp to terminal hairs, is indeed, possible.  However, there are still contradictory data, around the possibility of restoring healthy cycle back to miniaturized HFs. 


References

1. Garza LA, Yang CC, Zhao T, Blatt HB, Lee M, He H, et al. Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. J Clin Invest. 2011 Feb;121(2):613-22.

2. Krajcik RA, Vogelman JH, Malloy VL, Orentreich N. Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice. J Am Acad Dermatol. 2003;48(5):752-9.

3. Fenton DA, English JS, Wilkinson JD. Reversal of male-pattern baldness, hypertrichosis, and accelerated hair and nail growth in patients receiving benoxaprofen. Br Med J (Clin Res Ed). 1982;284(6324):1228-9.

----------


## NeedHairASAP

may a proteasome inhibitor?

J Biol Chem. 2002 Sep 27;277(39):36570-6. Epub 2002 Jul 15.
*Proteasome activity is required for androgen receptor transcriptional activity via regulation of androgen receptor nuclear translocation and interaction with coregulators in prostate cancer cells.*

Lin HK1, Altuwaijri S, Lin WJ, Kan PY, Collins LL, Chang C.

Author information

*Abstract*
Upon binding to androgen, the androgen receptor (AR) can translocate into the nucleus and bind to androgen response element(s) to modulate its target genes. Here we have shown that MG132, a 26 S proteasome inhibitor, suppressed AR transactivation in an androgen-dependent manner in prostate cancer LNCaP and PC-3 cells. In contrast, MG132 showed no suppressive effect on glucocorticoid receptor transactivation. Additionally, transfection of PSMA7, a proteasome subunit, enhanced AR transactivation in a dose-dependent manner. The suppression of AR transactivation by MG132 may then result in the suppression of prostate-specific antigen, a well known marker used to monitor the progress of prostate cancer. Further mechanistic studies indicated that MG132 may suppress AR transactivation via inhibition of AR nuclear translocation and/or inhibition of interactions between AR and its coregulators, such as ARA70 or TIF2. Together, our data suggest that the proteasome system plays important roles in the regulation of AR activity in prostate cancer cells and may provide a unique target site for the development of therapeutic drugs to block androgen/AR-mediated prostate tumor growth.
PMID: 12119296 [PubMed - indexed for MEDLINE] Free full text
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----------


## xyz123

Good luck FGF11 - we will be awaiting your return in 6-8 months  :Smile:   Your thread has gotten close to 10,000 views in less than 48 hours - which goes to show that you've gotten many people interested (not many journal articles can compete with those numbers  :Smile:  ).  

Pull this off and you'll grab the attention of the whole world - and become a billionaire in the process  :Smile:   And if you don't - that's OK too - I think we've all learned from your posts.

Here's to hoping that you return with good news in mid-2016!  :Smile:

----------


## youngin

FGF11 - You have definitely done your research. I for one appreciate the self starting science you are doing. However, I do not think your path will be successful. As you know, when someone has started balding and is castrated they will not grow all of the miniaturized hair back. There is only a MINIMAL amount of active androgens without testicles. There is more going on here than just androgens. Something is causing a calcification/scarring type effect and also damaging the DNA of the cells. This has all been published. For many people minoxidil works much better than Finasteride for growth stimulation, which has nothing to do with androgens, but probably has more to do with removal of the scar like tissue by being a calcium channel blocker and also limiting collagen formation.

----------


## pixels

I'm with Fred.

How many pages was that for pretty much no information.

You can't bring pics to the table for some kind of ethical condumdrum?

Oh please. You can waste our time with pages of mumbo jumbo but when somebody asks for evidence you get all holy.

No thanks. Please just go away.

----------


## Swooping

*@Chemical*

Thank you. See where I'm heading at though? Let's hypothetically assume that these factors are indeed deeply implicated in AGA. How does one work around that? Direct modulation of these factors for instance is something you can't really do I guess due to very serious safety concerns. I find it also interesting that 17b-estradiol can regrow hair to great extent sometimes but not always. I have seen pictures of people that have regrown a very big amount of hair due to being on anti-androgen therapy + estrogen. I think Cotsarelis puts this nicely again;




> Studies and case reports of transgender operations where men become women and receive high doses of estrogen show that a scalp that was almost completely bald can have, *after castration and high estrogen supplementation, a tremendous amount of hair growth.* The overall feeling is that the follicles can be thought of as being in three states. Either they’re terminal, and they’re large, or they’re miniaturized, and they’re small, and the hair they’re creating is microscopic, or they’re in between, called indeterminate. It’s thought that follicles reach a point where they’re producing a hair so small that at that point the chance of reversing that follicle is small. *There seems to be a point of no return with respect to androgen removal; even if you castrate someone who’s bald he won’t regrow all his hair. If you give him estrogen, too, he might.*


 When you look at what estrogen actions are on the hair follicle it's quite broad; http://press.endocrine.org/doi/full/...0/er.2006-0020. Awesome study in relation to estrogen and the hair follicle. Some targets seem to be the likes of Cyclin D1, AP-1 (c-fos , c-jun proto-oncogenes), SHH, WNT's etc. 

Does something stand out for you there? It does for me. All these targets of estrogen seem to be factors that control cell proliferation positively. And to no surprise estrogen is classified as a carcinogen and formulations of estrogen have a black box warning; http://www.cancer.org/cancer/cancerc...an-carcinogens. 




> Most of the actions of estrogens on the normal and abnormal mammary cells are mediated via estrogen receptors (ERs), including control of *cell proliferation*; however, there are also alternative pathways of estrogen action not involving ERs. Estrogens control several genes and proteins that induce the cells to enter the cell cycle (*protooncogenes, growth factors*); estrogens also act on proteins directly involved in the control *of the cell cycle (cyclins)*


 When we look at AP1 for example induction of it can repress (antagonize) other factors like P53, P16 , P21 etc;




> There is evidence that AP-1 proteins, mostly those that belong to the Jun group, *control cell life and death through their ability to regulate the expression and function of cell cycle regulators such as Cyclin D1, p53, p21cip1/waf1, p19ARF and p16.* Amongst the Jun proteins, *c-Jun is unique in its ability to positively regulate cell proliferation through the repression of tumor suppressor gene expression and function, and induction of cyclin D1 transcription. These actions are antagonized by JunB, which upregulates tumor suppressor genes and represses cyclin D1. An especially important target for AP-1 effects on cell life and death is the tumor suppressor p53, whose expression as well as transcriptional activity, are modulated by AP-1 proteins.*


 And all these factors P53, pRB, P21 etc. seem to act negatively on cell proliferation generally. Studies that I have shown that show these factors to be implicated in AGA. 

Now there is way more to read upon these pathways how they interact with each other obviously. So this begs the question how do we fix this problem? Well I can only think that you can guinea pig yourself and start modulating these factors directly. But as one can imagine that would be incredibly dangerous due to obvious reasons. 

To finish it off here are some examples where estrogen has regrown hair; 









And there are more cases. On another forum a transgender also is regrowing hair from NW5 to NW2. Doesn't happen always but it can happen. Estrogen is obviously no option though for any men  :Wink: . It's interesting nonetheless I guess. Perhaps you might find something. 




> *Swooping,* 
> 
> 1) Yes, they don't go bald (Castrated Males) Why? 
> 
> Since androgen as an initial signal is needed to get cells activated to produce cytokines in the first place. 
> 
> When androgen is totally absent cytokines, are not made in the HFs, and the eventual add up of cytokines therefore never happen. 
> 
> Now, imagine, when cytokines (or some other factors) levels are low, the activation of AR is majorly androgen dependent, while they start to add up, it become androgen independent, lessening and lessening the need for androgen-dependent signalling. 
> ...


 Thanks for your response. I get what you mean though. I don't agree with this entirely though. Again, even if you castrate someone who is aggressively balding his hair loss stops as I have said. So even when the process has been ongoing and these things add-up like you put it it doesn't matter. Cause when you remove androgens or AR balding will stop. Now finasteride might not always cut it, but after all finasteride doesn't remove all androgens as you very well know. RU-58841 doesn't sufficiently antagonize the androgen receptor either. Castration is better but not a really viable option I guess  :Wink: . After all that is why I don't think what you say will work. Sure full AR silencing will work excellent in preventing AGA, but will not do much more than castration. At least that is what I think. The thing is when you act to late these factors have already done their job like I mentioned. So removing AR out of the question doesn't matter anymore at this point. You used cancer cells as an example to point out the fact that these cells can find ways around to get stimulated. That's true but remember one hallmark of cancer cells is adaptation. They like to survive.




> Although targeting the androgen axis has clear therapeutic benefit, its effectiveness is temporary, as prostate tumor cells *adapt to survive and grow*.

----------


## youngin

I agree with Swoop that silencing AR is not going to do much more than stop the hair loss. The reason estrogen works may be because how it effects bone structures. It complete effect bone resorption as well as some forms of BMP. I bet the the transgender individuals ended up with skin changes as well, like being softer. Look at the bone structure difference in men and women, androgens have a huge affect on it. Even as an adult increasing androgens will increase bone density.

----------


## youngin

There are causes not being taken into consideration here. No one in this thread is addressing:
#1: Why does minoxidil work so well, and why does derma rolling increase its effectiveness. Look at PrettyFly83's results. This has nothing to do with androgens.
#2: Why does it present itself in a pattern. This has never been explained in a study.

----------


## NeedHairASAP

> *@Chemical*
> 
> So removing AR out of the question doesn't matter anymore at this point. You used cancer cells as an example to point out the fact that these cells can find ways around to get stimulated. That's true but remember one hallmark of cancer cells is adaptation. They like to survive.


 Swoop, what if estrogen down-regulates ARs? Then estrogen regrowing hair doesn't actually refute fg11's hypothesis.


http://www.ncbi.nlm.nih.gov/pubmed/3569146

----------


## gainspotter

Cute

----------


## joachim

yeah, fred doesn't know what he is talking about at all. of course, there are those side effects with minox. i've seen it in 4 of my friends who took it for months and then quit because of the sides in their face. swollen eyes and swollen face sometimes too, wrinkles and also headache from time to time. 
it's all placebo effect would fred say. he's just a typical mr. know-it-all and if he doesn't have side effects then nobody will.
fred is probably also one of those guys who says that Fin is absolutely side-effect free and that the sexual/hormonal side effects are not real.

all bullshit. fred it's not the right and place here for you. you're just spreading bullshit around, and also drove the FGF11 guy away. he was obviously one very intelligent bioscience guy who brought some good ideas in. it's not comparable with the typical con artists like habemus/futurocabeludo or the chlorine dioxine guy.

----------


## fred970

> i've seen it in 4 of my friends who took it for months and then quit because of the sides in their face. swollen eyes and swollen face sometimes too, wrinkles and also headache from time to time.


 That's just a harsh allergic reaction, of course it can happen.

But wrinkles? Show me one scientific study that proves minoxidil gives wrinkles or even dark circles?

Don't bother, you won't find any.

----------


## joachim

> That's just a harsh allergic reaction, of course it can happen.
> 
> But wrinkles? Show me one scientific study that proves minoxidil gives wrinkles or even dark circles?
> 
> Don't bother, you won't find any.


 lol. why on earth should there be studies out there which show the negative side effects of minox, and especially wrinkles and dark circles? of course we won't find them. but there are hundrets of reports/opinions/posts and pics on the internet, and if you just don't want to believe they exist, then be it so. everyone has the right to be ignorant and just believe what they want.

----------


## Chemical

> *@Chemical*
> Does something stand out for you there? It does for me. All these targets of estrogen seem to be factors that control cell proliferation positively. And to no surprise estrogen is classified as a carcinogen and formulations of estrogen have a black box warning; http://www.cancer.org/cancer/cancerc...an-carcinogens. 
> 
> When we look at AP1 for example induction of it can repress (antagonize) other factors like P53, P16 , P21 etc;
> 
> And all these factors P53, pRB, P21 etc. seem to act negatively on cell proliferation generally. Studies that I have shown that show these factors to be implicated in AGA. 
> 
> Now there is way more to read upon these pathways how they interact with each other obviously. So this begs the question how do we fix this problem? Well I can only think that you can guinea pig yourself and start modulating these factors directly. But as one can imagine that would be incredibly dangerous due to obvious reasons.


 I think we shouldnt mess around with p53 too much because it actually repairs DNA damage and we should be focusing on the detrimental byproducts of p53 which are ironically easier  to tackle, like DKK1 with oleuropein.

I've decided to post a an analysis on Estrogens actions on hair in my thread seeing as this thread is becoming a flame war and we're deviating from the main topic. I think youre on to something and we could potentially exploit the estrogen pathway with readily available/easily acquired drugs to achieve the same regrowth as those transgender cases.

https://www.baldtruthtalk.com/thread...l=1#post224562

----------


## youngin

> That's just a harsh allergic reaction, of course it can happen.
> 
> But wrinkles? Show me one scientific study that proves minoxidil gives wrinkles or even dark circles?
> 
> Don't bother, you won't find any.


 I already gave you multiple studies that correlate that in another thread as well as heart rate changes. It doesn't matter though, you are the biggest idiot I've ever seen on any forum perhaps. You are just here to bring negativity to everything with your stupidity.

----------


## fred970

> lol. why on earth should there be studies out there which show the negative side effects of minox, and especially wrinkles and dark circles? of course we won't find them. *but there are hundrets of reports/opinions/posts and pics on the internet*, and if you just don't want to believe they exist, then be it so. everyone has the right to be ignorant and just believe what they want.


 Because that's a reliable source of information. You're, everyone has the right to believe in BS. Just don't spread misinformation on the forum, that's all.

----------


## Steffyamola

what the guy wrote is interesting my dad had cancer of prostate and was on casodex before xtandi never had hair loss when he took xtandi he lost all his body hair neck down his skin became so sensitive and dry but he kept his head of hair and everyday he was so tired

----------


## sdsurfin

> what the guy wrote is interesting my dad had cancer of prostate and was on casodex before xtandi never had hair loss when he took xtandi he lost all his body hair neck down his skin became so sensitive and dry but he kept his head of hair and everyday he was so tired


 I don't know if this guy is out to eventually sell something or not, and a lot of what he writes is maybe true, but there are tons of broad and unproven statements in his argument against why other approaches will not work.  People like Cotsarellis are hugely informed about what compounds accelerate hair loss, and the fact that they are confident that PGD2 is a key is not independent of other knowledge about other cytokines. This guy writes as if its all or nothing. the fat is, if histogen or SM can stimulate growth enough and negate enough the chains set in place by the androgen receptor, then they can possibly be good enough to halt hair loss and cause some regrowth, which is enough for a lot of people.   Also, if they key is the androgen receptor then it doesn't negate replicel's approach to replacing follicle cells with androgen insensitive ones.  Also, just because DHT and possibly other cytokines activate the androgen receptor, doesnt mean that the condition cannot be treated downstream of that reaction.  

So I agree, no "cure" will come until you can genetically modify the androgen receptor's sensitivity OR replace our HF cells with dofferent ones (which is what replicel and other companies are working on, and in my opinion getting pretty close to achieving), but doing something like histogen is doing and activating the stem cells enough might be just as good and valid a long term treatment as whatever this dude is proposing, which seems much less safe and much less realistic.  The androgen receptor is taking the function out of the stem cells, so if you can boost those stem cells (and I disagree that researchers know very little about the signals, they actually know quite a lot, just listen to gail naughtons presentation on the factors that histogen works on)then why couldnt you override whatever the AR is doing?  

I'm not saying this isn't interesting and useful, I'm just saying you make some really sweeping statements and have little proof that what you tried is actually true or effective.  



PS minoxidil can def give you dark circles under your eyes. Every time i use it for any period of time this happens to me, and they go away when i stop the minox. can't be a coincidence, ive tried it too many times, and its very noticeable.  I have no idea about the wrinkles, but just cause a pharma company says theres no such side doesnt mean thats true. trials are flawed, they dont always look for such things and sometimes arent long enough.  just look at propecia. pretty sure the sides are way more common and severe than pharma claims, at least from my friends' experiences.

----------


## sdsurfin

Also, this guy proclaiming that he's leaving the forum and then saying that he's gonna go make it work, etc smells pretty weird to me.  If you're so confident about the potential in this, why don't you do your utmost to share it with researchers like cotsarellis and not with random internet people?  If this is so valuable then please, share it with the scientific community and the teams that are working to develop drugs.  it doesnt do anybody any good to share it with young and mostly clueless forum members.  If you can get a statement from christiano or cotsarellis or anyone who studies hairloss addressing your claims and your theory, then it would have much more weight.  I dont buy this being scared cause its not legal, you dont have to divulge your identity to anyone, on here or elsewhere.  write an anonymous email to a respected researcher from an anonymous account and let's see what they have to say....

----------


## Swooping

> I think we shouldnt mess around with p53 too much because it actually repairs DNA damage and we should be focusing on the detrimental byproducts of p53 which are ironically easier  to tackle, like DKK1 with oleuropein.
> 
> I've decided to post a an analysis on Estrogens actions on hair in my thread seeing as this thread is becoming a flame war and we're deviating from the main topic. I think youre on to something and we could potentially exploit the estrogen pathway with readily available/easily acquired drugs to achieve the same regrowth as those transgender cases.
> 
> https://www.baldtruthtalk.com/thread...l=1#post224562


 Ok thanks. Will reply later there  :Smile: . Indeed, P53 has a multi-faceted role, not everything of the pathway is known yet too!  Modulation of these pathways is obviously way too dangerous too. Anyway imo the picture is really getting more and more clear and would explain everything that correlates with AGA. Apoptosis? Cell cycle arrest? Senescence? ROS? DNA damage? Eventually we will get to know. 

Difference microRNA expression balding vs non-balding dermal papilla cells; 



Cell cycle;

----------


## Swooping

Couldn't edit last message wanted to add this; 




> P53 "guardian of the genome"


 


> RESULTS: *The frontal bald area of patients showed significantly higher levels* of X-ray Cross Complementing-1 (XRCC1; P<0.001) and *p53* (P<0.001) expression when compared with occipital hairy area of patients and frontal area of controls


 


> Molecular sensors respond to DNA damage signals by activating a sequence of events that leads to the execution of *cellular stress responses* (Levine 1997; Giono and Manfredi 2006; Laptenko and Prives 2006).
> In mammalian cells, the tumor suppressor* p53 is a master regulator of stress response pathways such as cell cycle checkpoints, DNA repair, senescence, and apoptosis*


 


> p53 is an evolutionarily ancient coordinator of metazoan stress responses.


 Senescence (this would explain the downstream inflammatory response);

----------


## eukaliptas

Sorry for my english. I registered to this forum just to say thank you, thank you IGF11 for your thoughts he has nothing to sell. I litteraly tried everything Proscar, Minoxidil, Dutasteride, even Spironolactone. First three did nothing, until i used the last one. I had regrowth, my scalp stoped itching and stoped producing excesive sebum, hair started getting thicker and thicker, i really felt great. But... I couldnt do cardio, i gained some extra weight and i think something happened to my nipples. And one day i had to quit spironolactone because after 5 or 6 months of usage in the middle of the night i woke up to such terrible testicular pain that i couldnt handle it anymore. It was litterally shutting down my ba**s. If i used it for one or two weeks more i probably ended being infertile. It was kids in the future and probably baldness or being infertile for the rest of my life so i quit. I read tons of research about spiro and i know how it works i understand the concept but i cant translate it to you because of my limited english. If i am correct 1. spiro bind to Androgen Receptors (if i am correct it prevents interaction with DHT and then it prevents all that messed up stuff happening in our Hair Follicle), 2. it catches all floating DHT in blood and 3. lastly it tries to shut down DHT Factory in the b***s. 

So what i want to say. After reading tons of research my idea is that DHT trigger Androgen Receptor it all starts here. And then normaly working hair follicle goes out of order because of genetical abnormalities (until we hit puberty everybody have great hair). It start to overproduce some elements (some pathways randomly activate some dont), also it shutdown some element production which then we lack also it starts overproducing shi*load sebum and we have broken Hair Follicle. So you have malfunctioning HF, infections and other stuf can happen in your scalp , what your body do now? It triggers Imune System to attack hair follicle, to kill it. Where does that terrible head itch come from? My idea its your body killing your own hair. Attack after attack, day after day it attacks your hair to minaturize and enter dormant phase. After your body makes that happen i feel no itch in those places i have no hair anymore.
After only one month of spiro, everything normalized in my scalp no ithch, no hair falling it even started growing small black hair (not all hair i lost but small amount) in my temple also sebum overproduction stoped. I cant understand why cant some scientist examine what happens in your scalp while on spiro i think it could give so answers.
IGF11 said that he lost all what he gained, my idea is that even after all those years your imune system is still in attack mode, you quit your treatment Imune system attacks it and kills it. If we want to stop hair minutirazation we have to suppress our imune system, if we want to completely prevent MPB we have to address Androgen receptor.  In earlier reply to thread one member mentioned immune suppressants, other mentioned Minutirized Human Hair Transplanted to Mice with no Imune System and those hair growing increadibly fast, Desmond when he visited hair loss congress which we all funded mentioned Singapore Scientists Group That specialize in approach which they try to affect Androgen Receptor (this group from singapore is in my head from the day1 i read that thread). So there is hope. Again sorry for my english

----------


## FGF11

Do you really think they care? I mean the researchers. 

Do you even know how scientific grants work. You write a whole grant, based on your previous publications, and then you show some preliminary data, and then you compete with a bunch of other people to get a grant that can possibly support you, may be, for the next 5 years or so. 

Do you know, scientists have to use bunch of previous money to produce that preliminary data, in the first place. 

Do you think I haven't tried to contact Dr. Cotsarelis? I think the guy is smart, but they are hugely restricted on what they can do and what they can’t do.

Do you know we live in a world of paradoxes?

Do you have any idea you have to wait at least four months until your protocol get accepted so you could do a tiny experiment on mice? Then we kill and eat at millions of millions of animals, much smarter than mice every year to eat and then die of hear attack. 

Do you know if today, you convince the whole world that silencing AR is way more effective than Finasteride and Minoxidil and Way more SAFE, and it works, you have to wait at least five to six years for it to hit the market, if EVER, because it will be expensive and not practical. 

Do you know I’m doubtful if anyone completely understood what I’ve written here.

Do you think I’m less knowledgable than them, the researchers. Just because I wrote my findings here. Do you think if I could have started my START-UP, I wouldn’t have done so. 

No, it’s ****ing hard. 

Time will convince people that I’ve been right or not. Or my next set of experiments. I was hoping I could find some knowledgeable people here, so I could keep in contact with them, and start doing something together.

Do you think when I said, I’m to going make it work, it's easy. Do you really know hard is it to really do so? 

I’m trying to culture E.Coli cells to make me enough amount of siRNA’s so I could test my hypothesis. Do you know how much reading I have done, and how planning I have done. Do you know how much work does that take. How much testing? Do you know how much of my own money I’m putting on this. 

Do you know about ego? and how it has killed so many advancements in the past.

Have you heard about United Therapeutics? the story behind its founder. GO READ IT.

Do you know the first people who found adult stem cells, have told the news SO MANY TIMES, that if some one came to them and propose to them iPSC cells, they would have never give the guy any money to do his experiments in the first place. iPSC cells have changed the world.

SCIENTISTS ARE FULL OF EGO.

Do you think if I could test my finding with experiments, I couldn't have done so.

Gosh jeez, some people here, don’t know the difference between a molecule and a cell phone. 

Do you think I care about other people? do you think they care about what I’ve written here? It’s a ****ing messed up world, do something. Don’t sit on your butt, man.

Sooner or later, someone will try what I’ve done here, the pharma and it will be known if it works or not. But I can’t wait for that time to come. Because science is slow, and biotech is greedy.

I believe in what I’ve done, based on what I’ve seen, it may end up NOT working, but at least in my spare time I have actually tried to impact my life, and MAY BE those around me.

I don’t have anything to sell, god, these people. 

Mark Zuckerberg, gives all his money to charity and just read the comments. Man, the world is SO messed up.

No reason, scientists don’t care to contact people directly, and ignore them like they are a plague. Watch the documentary life according to sam, watch the movie Lorenzo Oil, do you know how much criticism these people got. These are all true stories.

I'm just trying to my best people, and to me it makes sense more and more every day.

----------


## Hemo

That's all well and good...but don't you think, if you have pictures (as you claim you do), you would convince scientists, the public, and/or donors more easily if you showed that proof?

----------


## PatientlyWaiting

Sure pictures can help but it doesn't mean people have to be d*cks about it, brushing him off as a troll or trying to sell anything right off the bat in the very first page. Some people just like seeing the bad everyone, they don't give anyone the benefit of the doubt. Anyway, he says this is far away from even being done at all, so just the theory alone was interesting. What's pictures gonna do, make this thread another 50 page thread of members talking about how a better treatment is near 10 years from now? That is why I post on this site 2-3 times a year now, because every thread is all about treatments that are coming 5 years from now but then those treatments get pushed back to another 5-10 years. What happened to all those treatments that were being talked about, and there was pictures for them? They're not even mentioned here anymore. Pictures can mean something or they can mean nothing. His findings, in theory, are better than pictures. I mean i'm not going ot sit here and claim I understand everything the guy wrote, but I did read the entire thing and it was interesting and I kinda get the concept he is talking about.

----------


## Yaoza

]FGF11 or god..stay in touch with me . I am a  physician and your idea is very interesting..if it works for familial  cholesterol disorder..why can't it work for male pattern baldness...and some people aka Fred has the IQ of an ape....just because it is published in a journal he holds it as the gospel.....n when it is not in a journal he thinks it can never work..lol

I actually Think we should crowd fund n start a bio tech company...so there are like 10 scientist on the bench instead of just you working in the few hours after your day time job...like the movie extraordinary measurs u mentioned. ...everyone that believes in us donate some money , something small..like 100 to 500 dollars. The rest we get from IPO of the company going public.. We grant those who brought in some shares of this  comany and when this thing works..they also get free lifetime treatment cause every dude on earth will fork up like 100 bucks a month to have Brad Pitt hair until they r 70 years old

Some biotech will replicate this line of thought in like a few weeks/months ...word travel fast on the internet. ..probably the ones in china where there is less red tape...and no real IRB..lol..something along FGF11 's thought process should work n this is exciting. ..and this is good for bald dudes out there..including me :Smile:

----------


## Yaoza

Whatever happens though fgf11..patent your idea and protect your intellectual property..it may or may not work but it is your original idea

----------


## Justinian

Uhh... is this any different than what ASC-J9 is supposed to do? This is in the preclinical stage and is supposed to degrade the androgen receptor. I think people have tried it but I don't know the outcome and perhaps it wasn't penetrating if they did try it.

http://androscience.com/ard_pub.php

"ARD enhancer compounds are believed to alter the tertiary structure of the AR protein upon encountering the receptor in the cytoplasm. This results in the disassociation of AR from its chaperon proteins and subsequently leads to loss of structural integrity, drastically reducing AR activation by its ligand, androgens. The alteration of AR tertiary structure and limited binding ability with stabilizing chaperone proteins makes the AR vulnerable to ubiquitination and degradation via the proteasome-mediated pathway."

"ARD Enhancers represent a completely novel Mechanism of Action (MOA) which target a known, validated nuclear receptor implicated in a variety of disease states. The MOA has significant advantages over conventional drugs which lower the levels of endogenous ligands such as testosterone or dihydrotestosterone (DHT) and other related steroids. *ARD Enhancers selectively reduce the AR and its gene control activity, even in the presence of androgens. Through reducing AR protein levels, an ARD enhancer approach overcomes the impact of AR activation by non-androgen (or non-genetic) ligand pathways and unlike conventional anti-androgens ARD Enhancer compounds possesses no partial agonistic activity*."

That bolded part seems to agree with this guy's theory about non-androgen AR activation.

----------


## Hairmore

> Whatever happens though fgf11..patent your idea and protect your intellectual property..it may or may not work but it is your original idea


 That would be the first time someone would would be sharing some break-trough science in an online forum instead of some medical paper. I hope this is really good but it all seems a bit not serious to me.

----------


## TheKingofFighters

hi so is the AR inhibitor u're talking about the cure?

----------


## Kokles

Is it so hard to take and post pictures? A visible improvement in hair density is what we're after. I've had insanely great results with minoxidil alone.. even smudgy old phone photos shown massive overall increase in density.

Swiss posted pictures and they are beyond laughable.. he also thinks he "hacked" it

----------


## Kokles

Is it so hard to take and post pictures? A visible improvement in hair density is what we're after. I've had insanely great results with minoxidil alone.. even smudgy old phone photos shown massive overall increase in density.

Swiss posted pictures and they are beyond laughable.. he also thinks he "hacked" it

----------


## fred970

> Is it so hard to take and post pictures? A visible improvement in hair density is what we're after. I've had insanely great results with minoxidil alone.. even smudgy old phone photos shown massive overall increase in density.
> 
> Swiss posted pictures and they are beyond laughable.. he also thinks he "hacked" it


 This, it would be so easy to post results if these people had any.

----------


## Hemo

> Sure pictures can help but it doesn't mean people have to be d*cks about it, brushing him off as a troll or trying to sell anything right off the bat in the very first page. Some people just like seeing the bad everyone, they don't give anyone the benefit of the doubt. Anyway, he says this is far away from even being done at all, so just the theory alone was interesting. What's pictures gonna do, make this thread another 50 page thread of members talking about how a better treatment is near 10 years from now? That is why I post on this site 2-3 times a year now, because every thread is all about treatments that are coming 5 years from now but then those treatments get pushed back to another 5-10 years. What happened to all those treatments that were being talked about, and there was pictures for them? They're not even mentioned here anymore. Pictures can mean something or they can mean nothing. His findings, in theory, are better than pictures. I mean i'm not going ot sit here and claim I understand everything the guy wrote, but I did read the entire thing and it was interesting and I kinda get the concept he is talking about.


 Yes, but his/her last post was largely about the amount of effort that goes into this kind of research/discovery, only to be snubbed by the scientific community and public.  If there's proof (e.g. pictures), that is one hell of a way to convince people.  

Even if we knew it would take another 5-10 years, at least we know it's coming.

----------


## sdsurfin

You ranted a lot about the scientific process but did not address any one of my points about your science.  Also, propecia is very effective at stopping hair loss in most people who take it (like 80 percent or something). If non-androgen compounds were so important to turning on the AR and the balding process, then why is this true? Also again, why does your theory imply that replicel "won't work"? if the problem lies in the AR, then surely replacing AR sensitive cells with new ones is a good idea. So is something like histogen which essentially drowns out the AR's signals.  You make very sweeping statements about what will and wont work, and then show no proof that your ideas work at all.   It's very hard to take any of this seriously when you have no evidence, even if your idea is legit, which it might be.  How is this supposed to be useful to anyone if you don't put it into action?   I don't think you're trying to make money (though maybe you should be).  If you have proof that it works and can get hair scientists to back you up, I'm sure with some effort you could get things rolling somewhere, even if its japan or europe and not is the US.

----------


## jamesst11

> You ranted a lot about the scientific process but did not address any one of my points about your science.  Also, propecia is very effective at stopping hair loss in most people who take it (like 80 percent or something). If non-androgen compounds were so important to turning on the AR and the balding process, then why is this true? Also again, why does your theory imply that replicel "won't work"? if the problem lies in the AR, then surely replacing AR sensitive cells with new ones is a good idea. So is something like histogen which essentially drowns out the AR's signals.  You make very sweeping statements about what will and wont work, and then show no proof that your ideas work at all.   It's very hard to take any of this seriously when you have no evidence, even if your idea is legit, which it might be.  How is this supposed to be useful to anyone if you don't put it into action?   I don't think you're trying to make money (though maybe you should be).  If you have proof that it works and can get hair scientists to back you up, I'm sure with some effort you could get things rolling somewhere, even if its japan or europe and not is the US.


 propecia is not 80% effective in stopping hair loss... that's complete BS

----------


## Tenma

> propecia is not 80% effective in stopping hair loss... that's complete BS


 youre right james, propecia stops the balding process in 90+ percent of people, not only 80% LOL

http://www.ncbi.nlm.nih.gov/pubmed/21910805

----------


## doinmyheadin

> You ranted a lot about the scientific process but did not address any one of my points about your science.  Also, propecia is very effective at stopping hair loss in most people who take it (like 80 percent or something). If non-androgen compounds were so important to turning on the AR and the balding process, then why is this true? Also again, why does your theory imply that replicel "won't work"? if the problem lies in the AR, then surely replacing AR sensitive cells with new ones is a good idea. So is something like histogen which essentially drowns out the AR's signals.  You make very sweeping statements about what will and wont work, and then show no proof that your ideas work at all.   It's very hard to take any of this seriously when you have no evidence, even if your idea is legit, which it might be.  How is this supposed to be useful to anyone if you don't put it into action?   I don't think you're trying to make money (though maybe you should be).  If you have proof that it works and can get hair scientists to back you up, I'm sure with some effort you could get things rolling somewhere, even if its japan or europe and not is the US.


 What happened with Follicept?

----------


## xHELLSEHERx

> youre right james, propecia stops the balding process in 90+ percent of people, not only 80% LOL
> 
> http://www.ncbi.nlm.nih.gov/pubmed/21910805


 It didn't help me at all! To see any result you need 3 to 6 months, then after 1/2 years it does not work for most guys. That is my observation. Maybe wrong, or right!

----------


## Spaceboy

Yeah, the 90+% wake up feeling like shit and can't get it up/gyno  too. Fin definitely can help/work to halt or slow the inevitable , but for a lot of people that comes at a steep price.

----------


## jamesst11

> youre right james, propecia stops the balding process in 90+ percent of people, not only 80% LOL
> 
> http://www.ncbi.nlm.nih.gov/pubmed/21910805


 I have thoroughly read hundreds of research papers and published articles through my 6 years attaining my masters degree in cellular and molecular bio, and have even published two myself.  I know for a fact that this is complete bullshit.

----------


## jamesst11

I would say that propecia HELPS MAINTAIN in 50-60% of people who regularly use it and can bare the side effects.  That is more accurate.

----------


## Justinian

> I would say that propecia HELPS MAINTAIN in 50-60% of people who regularly use it and can bare the side effects.  That is more accurate.


 Do you have facts to back that up with?

----------


## jamesst11

nope, that's why I prefaced that statement with, "i would say"... believe what you want to man,  but 80-90% is WAY OFF.

----------


## Justinian

> nope, that's why I prefaced that statement with, "i would say"... believe what you want to man,  but 80-90% is WAY OFF.


 Are you basing that off of what you see on here? Forums like this are definitely biased towards the 10% it doesn't work on.

----------


## fred970

And, this thread is already sinking and going nowhere.

----------


## NeedHairASAP

> And, this thread is already sinking and going nowhere.


 Review your posts. Wasn't that your goal?

----------


## UNBEAT

thanks fgf11 for what you are doing.. i wanted to know if your cure can help with seborreah severe hair loss .i have lost most of my hair because of it. thank you

----------


## fred970

> Review your posts. Wasn't that your goal?


 My goal? Yeah right. This thread is dead. Value = 0.

----------


## bananana

> My goal? Yeah right. This thread is dead. Value = 0.


 ok, thank you for your deep insights fred.
you can walk away from this thread then. 

bye.

----------


## fred970

> ok, thank you for your deep insights fred.
> you can walk away from this thread then. 
> 
> bye.


 Everyone has walked away from this thread, unsurprisingly.

----------


## bboyforever

The guy comes on with a detailed and seemingly plausible theory. Some people objected to his theory, other's demanded proof. He defended himself to a point and said he'd try his theory out and report back in some months. There's not really a lot left to say. No one can really try at what he's doing because he's using way more advanced equipment and knowledge than anyone else here, and the only people knowledgeable enough to critique his theory in any meaningful way have already done so.

You're not bursting other people's delusions fred, you're just trying to bolster your own. Take control of yourself man.

----------


## Westonci

> Do you really think they care? I mean the researchers. 
> 
> Do you even know how scientific grants work. You write a whole grant, based on your previous publications, and then you show some preliminary data, and then you compete with a bunch of other people to get a grant that can possibly support you, may be, for the next 5 years or so. 
> 
> Do you know, scientists have to use bunch of previous money to produce that preliminary data, in the first place. 
> 
> Do you think I haven't tried to contact Dr. Cotsarelis? I think the guy is smart, but they are hugely restricted on what they can do and what they can’t do.
> 
> Do you know we live in a world of paradoxes?
> ...


 
Please dont give up or listen to fred970.

I really appreciate the hard work you put into this, and I know you are on to something. We need knowledgeable people like you to lead the way. 

Tesla, Einstein, Turing etc. We live the way we do today because the legacy these guys have made.

If you can crack this, you will go down in history and will be among the giants of history that changed everything.

God speed fgf11

----------


## FGF11

Update #1:

My theory was not completely correct, however, the approach remains the same. 

I’ve come to the conclusion, based on two other experiments I did, that AR cytoplasmic retention (and not its nuclear localization) is the cause of irreversible hair follicle miniaturization. 
In epidermal and dermal cells, beta-catenin binds to androgen receptor in a DHT dependent manner. This also occurs, in small amounts, in DHT independent manner. This blocks beta-catenin and therefore, do not let it bind co-transcription factors. 

There is a pool of cytoplasmic beta-catenin that competes with cytoplasmic androgen receptor. When, overtime, levels of AR (HF miniaturization) goes beyond the levels of cytoplasmic beta-catenin, it stop beta-catenin from acting. Therefore, cells stay in a catagen-like state, in another word, miniaturized. AR per se does not cause damage, in a sense that it’s irreversible, as AR is super active in other HFs such as beards or pubes.

The balance (number of beta-catenin and Androgen Receptors), however, is critical for HF miniaturization to be reversible, the moment the balance is won by AR, HF miniaturization is no longer reversible. This happens when baldness advances, to a degree that AR expression is beyond the levels of cytoplasmic beta-catenin.

Therefore, HFs stay in a doomed cycle, as they can not get out of miniaturization, since it requires beta-catenin to regenerate, and no matter how you activate it, beta-catenin is locked down either in nucleus by androgen-bound AR (as it can't bind TCF/LEF1 when bound to AR) or in the cytoplasm (even in a DHT independent manner due to its phosphorylation by detrimental cytokine signals).

Now, binding of AR to AR antagonist (pure or non-pure) most probably will not change its affinity for beta-catenin, it may, however, stop its nuclear localization. Therefore, no AR antagonist, as of now, is able to reverse HF miniaturization.

#Update 2: 

I have now bought tobacco plants, and I am trying to engineer them into producing large-amounts of potent siRNA’s. I am still facing lots of problems, however, if there are some biologists here (or if you know people who have the knowledge and might be interested), who know how to do simple wet lab experiments with either bacteria or plants, and do like to participate in something that can change the world and believes in the same philosophy that I believe in (open science, and the fact that scientists put their pants on just like you and me), contact me. I am the most unashamedly ambitious person who wants to get rid of this thing once and for all.

Please, unless you are contributing something valuable to this thread, don't post.

----------


## FGF11

This, I would say, is no longer a theory, and I have high confidence, it is true.

----------


## FGF11

I'm also thinking about taking this discussion off this forum (maybe reddit), as, clearly, in retrospect, this place was not a good place to start this. May be someone can design a website for this. I appreciate your support and encouraging words. Life is short, and I'm trying to justify my existence here. It's okay to ask questions though.

----------


## Link Mahboi

> I'm also thinking about taking this discussion off this forum (maybe reddit), as, clearly, in retrospect, this place was not a good place to start this. May be someone can design a website for this. I appreciate your support and encouraging words. Life is short, and I'm trying to justify my existence here. It's okay to ask questions though.


 FGF11, do you believe it's possible to reverse follicle DNA damage?

----------


## Seuxin

Some peptides can reverse dna damage.
Maybe cooper peptides from Dr Loren Pickard !
( It's not advertissment...i just told..."maybe" )

----------


## Keeper

yes please create a web page FGF11 ! would love to follow you

----------


## Westonci

> yes please create a web page FGF11 ! would love to follow you


 Its better to make a subreddit on reddit. Its better for discussions.

https://www.reddit.com/r/CuringBaldness/

FGF11 Ill make you a mod of the sub.

----------


## Westonci

> #Update 2: 
> 
> I have now bought tobacco plants, and I am trying to engineer them into producing large-amounts of potent siRNA’s. I am still facing lots of problems, however, if there are some biologists here (or if you know people who have the knowledge and might be interested), who know how to do simple wet lab experiments with either bacteria or plants, and do like to participate in something that can change the world and believes in the same philosophy that I believe in (open science, and the fact that scientists put their pants on just like you and me), contact me. I am the most unashamedly ambitious person who wants to get rid of this thing once and for all.








Does the siRNA deactivate the androgen receptor? if so how?

Would a needle be enough, or do we need to use viruses?

----------


## Seuxin

Why not using a website like Linkedin in order to find bald peopl who have labs experiment in order to help you ?

----------


## jjo

Keep at it guys.. appreciate your time and effort.. don't let the dinks like Fred stop you

----------


## Marconi SK

WoW FGF11 our savior/Messiah

----------


## Kokles

> WoW FGF11 our savior/Messiah


 Extraordinary claims require extraordinary evidence...

----------


## Sogeking

If FGF11 has the means and knowledge to test his theories let him try them. Even if he fails we will still learn something. That is what science is about. And only through science will we get to the cure.

----------


## BaldingEagle

I wish you the best in your research.

Fred tends to be very close minded, pay his negativity no mind. If scientists thought like him we'd never have any new treatments for anything.

----------


## Not giving up

'If I'd asked people what they wanted they would have said faster horses.' - Henry Ford. 

I may not believe in all this 100%, but if you're legit, good luck, I pray you're on to something useful.

----------


## youngin

FGF11 - I appreciate all the work you are doing. Can you please address my question though. Why would AR issues cause balding in a pattern? Why would minoxidil be the BEST growth stimulator if the problem was purely AR? It doesn't add up. Dermarolling + Minoxidil are far better growth stimulators than Finasteride will ever be.

----------


## pixels

> FGF11 - I appreciate all the work you are doing. Can you please address my question though. Why would AR issues cause balding in a pattern? Why would minoxidil be the BEST growth stimulator if the problem was purely AR? It doesn't add up. Dermarolling + Minoxidil are far better growth stimulators than Finasteride will ever be.


 ftw111 doesn't even know if it's going to work on himself yet.

We don't even know if fgf11 is legit yet (yup need photos).

----------


## BaldingEagle

> FGF11 - I appreciate all the work you are doing. Can you please address my question though. Why would AR issues cause balding in a pattern? Why would minoxidil be the BEST growth stimulator if the problem was purely AR? It doesn't add up. Dermarolling + Minoxidil are far better growth stimulators than Finasteride will ever be.


 Finasteride can do far more for miniaturization regrowth than minox or derma rolling could ever hope to in people with somewhat recent loss and no actual bald spots.

Derma rolling is also extremely uncomfortable and leaves you looking ridiculous and in pain.

I do like minox added to a DHT blocker though.

The sad truth is until there is a real breakthrough NW4 and up are just screwed outside of a HT. No amount of derma rolling and minox is going to take you back to NW2 or better. Maybe a deep NW3.

----------


## Onion Knight

> Do you really think they care? I mean the researchers. 
> 
> Do you even know how scientific grants work. You write a whole grant, based on your previous publications, and then you show some preliminary data, and then you compete with a bunch of other people to get a grant that can possibly support you, may be, for the next 5 years or so. 
> 
> Do you know, scientists have to use bunch of previous money to produce that preliminary data, in the first place. 
> 
> Do you think I haven't tried to contact Dr. Cotsarelis? I think the guy is smart, but they are hugely restricted on what they can do and what they cant do.
> 
> Do you know we live in a world of paradoxes?
> ...


 Thanks to share your knowledge. Some people here are like virus who try to suck positivity of person who still have faith. Is your treatment is working or no? Photo or no? So what man you try to do something people who dislike you should not come here and say you make them lost their time they are making lose your time.

Some are immature I know that Fred is popular and he claim that he want to prevent people by losing time or buying false treatment but shit this guy never answer to my comment I ask him for his help a lot of time still I respect him and like how he think but god he never answer me we suppose to help each other here. It's true that many people come here and fake treatment and some want to help but they doesn't do it right and got angry lol... Fred got scam I understand that but he should let people share their knowledge.

And it's true scientist or high doctor are full of ego... They think they know everything and treat you like shit. I got a injury and when I try to give my opinion on it they decline it and say it's can't be that cuz he just doesn't care. Still I never get healed.

Continue posting and sharing. But I wonder if none of theses treatment work and if your treatment is really expensive and not confirmed yet what should we do now is there anything we can do!?

----------


## NeedHairASAP

> Thanks to share your knowledge. Some people here are like virus who try to suck positivity of person who still have faith. Is your treatment is working or no? Photo or no? So what man you try to do something people who dislike you should not come here and say you make them lost their time they are making lose your time.
> 
> Some are immature I know that Fred is popular and he claim that he want to prevent people by losing time or buying false treatment but shit this guy never answer to my comment I ask him for his help a lot of time still I respect him and like how he think but god he never answer me we suppose to help each other here. It's true that many people come here and fake treatment and some want to help but they doesn't do it right and got angry lol... Fred got scam I understand that but he should let people share their knowledge.
> 
> And it's true scientist or high doctor are full of ego... They think they know everything and treat you like shit. I got a injury and when I try to give my opinion on it they decline it and say it's can't be that cuz he just doesn't care. Still I never get healed.
> 
> Continue posting and sharing. But I wonder if none of theses treatment work and if your treatment is really expensive and not confirmed yet what should we do now is there anything we can do!?


 
What people don't get is that he is using patented chemicals and he could never profit from this... at most maybe the company who owns the patent may hire him to work on it. But this guy can not sell his treatment to us (for a number of reasons). 

MAYBE he could try to do black market sales of this, but if he really has even a mediocrity successful career as of now, it makes no sense for him to try and start a black market checmical company in china... 

which means he is just some guy with access to lab equipment who is willing to give some experimental stuff a try out of general curiosity and a want to solve this bald problem... 

So I don't get why people are acting like he "needs to show proof" as if he is trying to sell this to us... yes... showing pictures etc. would be awesome... but this is not the same situation as say... histogen.... who is soliciting investor funds and trying to sell something... they VERY MUCH need to show proof.

So, lets give it a break.

----------


## youngin

> Finasteride can do far more for miniaturization regrowth than minox or derma rolling could ever hope to in people with somewhat recent loss and no actual bald spots.
> 
> Derma rolling is also extremely uncomfortable and leaves you looking ridiculous and in pain.
> 
> I do like minox added to a DHT blocker though.
> 
> The sad truth is until there is a real breakthrough NW4 and up are just screwed outside of a HT. No amount of derma rolling and minox is going to take you back to NW2 or better. Maybe a deep NW3.


 #1 - Finasteride nor any androgen based therapy is going to regrow the amount of hair possible with Minoxidil. As already mentioned, castration only stops hair loss... it doesn't act as ultimate regrowth.
#2 - If dermarolling is extremely uncomfortable you are doing it wrong. It does not have to be as aggressive as some people make it.
#3 - You have not followed the long term dermarolling progress. PrettyFly83 went from a NW6 to almost a NW3. In this study men on Finasteride AND Minox for 2-5 years were at a stand still and started regrowing more hair after adding dermarolling:
http://www.ncbi.nlm.nih.gov/pubmed/26120151

Everyone on this forum is far underestimating it because of dumbasses like fred. No one is doing long term runs with the correct supplements for skin support (MSM / Vitamin C / Zinc).

----------


## fred970

> No one is doing long term runs with the correct supplements for skin support (MSM / Vitamin C / Zinc).


 None of these will regrow a single hair. Show me one before/after picture, just one! I can show you thousands for minoxidil/finasteride/hair transplants.

----------


## youngin

> None of these will regrow a single hair. Show me one before/after picture, just one! I can show you thousands for minoxidil/finasteride/hair transplants.


 Apparently you can't read. I didn't say they alone would regrow a single hair. Go away you troll.

----------


## NeedHairASAP

> #1 - Finasteride nor any androgen based therapy is going to regrow the amount of hair possible with Minoxidil. As already mentioned, castration only stops hair loss... it doesn't act as ultimate regrowth.
> #2 - If dermarolling is extremely uncomfortable you are doing it wrong. It does not have to be as aggressive as some people make it.
> #3 - You have not followed the long term dermarolling progress. PrettyFly83 went from a NW6 to almost a NW3. In this study men on Finasteride AND Minox for 2-5 years were at a stand still and started regrowing more hair after adding dermarolling:
> http://www.ncbi.nlm.nih.gov/pubmed/26120151
> 
> Everyone on this forum is far underestimating it because of dumbasses like fred. No one is doing long term runs with the correct supplements for skin support (MSM / Vitamin C / Zinc).


 
I actually got results from zinc. I'm not sure it will work for everyone, maybe I was severely deficient.

It mostly filled in the "sideburn to temple" thinning area that you see on some people. I think I read somewhere that that area in particular is where you thin if you're iron deficient-- so maybe zinc deficiency is a similar situation.

I'm not saying zinc can substitute fin but it gave me (potentially) actual cosmetic regrowth... I'd say it's worth everyone getting on a zinc supplement. It has benefits beyond potentially be good for your hair.

----------


## Ulti1

Wish I could help you.  Realistically, The only thing I really could do for you is build you a site.

Unless you want me to come to your lab and pretend like I'm working on tobacco plants by watching "how to do science experiments " on youtube.  Which would probably end in me getting frustrated and trying to smoke the plant.

id atleast need to be payed 2$ an hour and bum on your couch though.  Let's do it! Haha

----------


## pixels

> Apparently you can't read. I didn't say they alone would regrow a single hair. Go away you troll.


 Apparently you're in the wrong forum.

Here we want to see cutting edge treatments with photographic evidence and results.

I am grateful for this guys work but i've been here for about 8 years (lost my old account) and Ill always lobby for proof. Words are cheap. Even the fancy long spiels.

----------


## youngin

> Apparently you're in the wrong forum.
> 
> Here we want to see cutting edge treatments with photographic evidence and results.
> 
> I am grateful for this guys work but i've been here for about 8 years (lost my old account) and Ill always lobby for proof. Words are cheap. Even the fancy long spiels.


 The OP never said he had proof of anything or that he even accomplished anything. My comments were about dermarolling and proof has already been given to that. I would say going from a NW6 to a NW3 is pretty cutting edge though. The best thing about OP is that hes actually using his brain and trying things. This isn't the best place to report it because of all the negativity around anything other than the big 3.

----------


## youngin

> I actually got results from zinc. I'm not sure it will work for everyone, maybe I was severely deficient.
> 
> It mostly filled in the "sideburn to temple" thinning area that you see on some people. I think I read somewhere that that area in particular is where you thin if you're iron deficient-- so maybe zinc deficiency is a similar situation.
> 
> I'm not saying zinc can substitute fin but it gave me (potentially) actual cosmetic regrowth... I'd say it's worth everyone getting on a zinc supplement. It has benefits beyond potentially be good for your hair.


 I agree. There are multiple studies showing how Zinc affect 5AR. It most definitely regulates it. Most people on this board should be supplementing with it as the dietary amount we get is very little in a Western diet. To re-iterate what you said, no one is claiming it can destroy 5AR the way that Finasteride does.

----------


## FGF11

> FGF11 - I appreciate all the work you are doing. Can you please address my question though. Why would AR issues cause balding in a pattern? Why would minoxidil be the BEST growth stimulator if the problem was purely AR? It doesn't add up. Dermarolling + Minoxidil are far better growth stimulators than Finasteride will ever be.


 Hey, Tnx.

Take a look at this:


This is the expression profile of AR and 5-AR, 

what you notice is that Occipital part of the Scalp and Frontal part of the Scalp have differential AR and 5-AR expression. It means that, for some epigenetic reasons, AR and 5-AR are not expressed in frontal scalp.

This is why in GWAS studies, you see HDAC proteins and PAX (a homeobox) proteins show up. HDAC proteins are epigenetic modulators, in a sense they cause gene to go silent or get expressed. In this cases, developmental changes cause different expression patterns in people with AGA, and so because of HDACs gene expression profiles change. This change cause further immunogenetics responses that you see.


As I told you, frontal scalp is developmentally different from occipital scalp. 

Imagine your fingers (toe and thumbs), they look kind of the same, right? but they are actually different. 

Same as occipital and frontal region of the head. So, since they are developmentally different, they act and age differently. 

So, that's the reason there is a pattern. 

Maybe evolutionary, it was advantageous.

As for why Minoxidil works in both males and females is this: 

Minoxidil works, I suppose, because it helps the release of beta catenin. 

Now, its mode of action is different from Lithium Chloride. 

It releases beta-catenin, maybe, by simply inhibiting its binding (or GSK-3) to AR (it also binds AR). Now, lithium Chloride can't do that, or any external beta-catenin stimulator (to a degree). 

To get a better sense of what I'm sating, imagine, AR is the main cause of miniaturization and Beta-catenin is needed for regrowth (It's very simple explanation but helps my discussion), so for already miniaturized follicles AR nuclear inhibition can't help, because, they need beta-catenin, to go in anagen. 

However, beta-catenin activation in already saturated cytoplasmic AR is impossible, as both GSK-3 and Beta-catenin are modulated by AR, and AR inhibits their action. 

Derma-rolling might help, (I'm not a fan) by increasing growth stimulants, and it works better with Minox, I guess, just because it helps it's absorption. 

One more thing, you need to know is that AR expression cause lineage differentiation of keratinocytes toward sebaceous gland, so basically, just stopping AR will stop oily and itchy scalp as well. 

I tried to explain it simply, hope that helps. You can search for references yourself, as I didn't have time to put it here.

----------


## FGF11

Yongie: also read this: http://www.ncbi.nlm.nih.gov/pubmed/22283397

* It means that, for some epigenetic reasons, AR and 5-AR are not expressed in occipital scalp.

----------


## youngin

> Yongie: also read this: http://www.ncbi.nlm.nih.gov/pubmed/22283397


 I cannot read the full article of the study your image and information about 5aR was pulled from but this study: http://press.endocrine.org/doi/full/...jcem.86.6.7545 references the one you pulled from and says:



> In addition, AR mRNA was found to be expressed at a higher level in cultured DP cells from androgen-responsive hair follicles, such as beard and axillary hairs, than in those from follicles of occipital hairs (22). However, we failed to detect any quantitative differences in terms of the level of expression of AR mRNA in DP cells between balding and nonbalding scalp....We did not find any differences in terms of the expression of AR, 5αR1 and 5αR2 mRNAs, or in terms of 5αR activity between hair follicles from balding and nonbalding scalp.


 I am inclined to have to ignore the science around this because I have seen many different variations of this in papers. There more, there's not more, 5aR or AR, its only in the DP, no its in the whole follicle. I will look into Minoxidil's action on Beta-Catenin further but I do not currently believe this is the method of action it uses. 

If all of this AR talk was true you should be able to reverse all hair loss by castration and we both know that doesn't work. There is not enough meaningful testosterone in the body after that to continue to cause balding, yet it cant reverse it all... this should tell you something else is happening completely independent of testosterone. Multiple studies have shown the scarring/fibrosis that happens after miniaturization, and I don't see how your solution would solve that. However, it makes sense that Minoxidil and rolling would solve that.

----------


## FGF11

> I cannot read the full article of the study your image and information about 5aR was pulled from but this study: http://press.endocrine.org/doi/full/...jcem.86.6.7545 references the one you pulled from and says:
> 
> I am inclined to have to ignore the science around this because I have seen many different variations of this in papers. There more, there's not more, 5aR or AR, its only in the DP, no its in the whole follicle. I will look into Minoxidil's action on Beta-Catenin further but I do not currently believe this is the method of action it uses. 
> 
> If all of this AR talk was true you should be able to reverse all hair loss by castration and we both know that doesn't work. There is not enough meaningful testosterone in the body after that to continue to cause balding, yet it cant reverse it all... this should tell you something else is happening completely independent of testosterone. Multiple studies have shown the scarring/fibrosis that happens after miniaturization, and I don't see how your solution would solve that. However, it makes sense that Minoxidil and rolling would solve that.


 Okay, I explain a little more about castration: 

Look, What is the role of castration? You take the balls out. Right? no testosterone anymore. So basically no DHT anymore. And no further miniaturization right. please read my writing as intelligently as possible. Miniaturization is DHT dependent. So you basically stop hair loss. No more DHT and testosterone binds the AR, so it can't get into the nucleus and drive miniaturization. But you're not inhibiting cytoplasmic AR, which, binds Beta-catenin either in presence of DHT or absence of DHt. Castration do not reduce AR expression levels. So, you won't see regrowth. Beta-catenin can't act in presence of AR. The binding of AR and beta-catenin is no completely DHT dependent. It's explained in the link I sent you.

----------


## youngin

Also I would like to point out that correlation is not causation. Even if your study was 100% right about 5aR expression then beard hairs would be just as likely to bald. You may just be trying to prove that theres a differentiation between bald vs non-bald follicle's genetically, but I don't see how this puts blame on androgens. Too much other research has been done on epigenetic factors, effect of cytokines, skin formation, etc. My bet is that Cyclosporine would grow just as much or more hair than any androgen suppressor.

----------


## FGF11

> Also I would like to point out that correlation is not causation. Even if your study was 100% right about 5aR expression then beard hairs would be just as likely to bald. You may just be trying to prove that theres a differentiation between bald vs non-bald follicle's genetically, but I don't see how this puts blame on androgens. Too much other research has been done on epigenetic factors, effect of cytokines, skin formation, etc. My bet is that Cyclosporine would grow just as much or more hair than any androgen suppressor.


 Cyclosporine A is interesting. the thing is you should differ between, AGA and normal hair regrowth. Put them in tow different categories. There are some reagents that grow hair, on every follicle. Like Cyclosporine A, (cause hirsutism) or Minoxidil. And there are drugs, that have differential characteristics (what is interesting for AGA) like androgen inhibitors, or AR inhibitors. 

So yes, even though Cyclosporine A will grow hair, and Dr. Paus studies show that. It will never be effective for AGA. I got to go, Read a little more, and ask questions if you came across them.  :Smile:

----------


## joachim

> Okay, I explain a little more about castration: 
> 
> Look, What is the role of castration? You take the balls out. Right? no testosterone anymore. So basically no DHT anymore. And no further miniaturization right. please read my writing as intelligently as possible. Miniaturization is DHT dependent. So you basically stop hair loss. No more DHT and testosterone binds the AR, so it can't get into the nucleus and drive miniaturization. But you're not inhibiting cytoplasmic AR, which, binds Beta-catenin either in presence of DHT or absence of DHt. Castration do not reduce AR expression levels. So, you won't see regrowth. Beta-catenin can't act in presence of AR. The binding of AR and beta-catenin is no completely DHT dependent. It's explained in the link I sent you.


 hey FGF11, nice work. we have some members here who somehow have a deeper background about biology and chemistry but for the first time i have a feeling that with you we have a real scientist here finally. you seem to know how stuff works and also have access to tools and equipment to test different theories. that's fantastic. i really think you could be onto something and even if some your thoughts turn out as wrong, i feel you can help greatly to understand the AGA mechanism and maybe even find some solution to it.
i strongly believe that if more members like you would take things into their own hands, we would already have a solution or at least better treatment options. 
it would highly suggest that you let someone set up a site or blog for you where you can summarize and share your findings. an open science community would definitely accelerate the process in finding treatments for AGA. i'm not at all relying on the hairloss researchers like cotsarelis and others. they might have good knowledge and experience but they are not eager enough to really solve problems. they are tinkering around in their labs for decades without significant progress. an open science with knowledgeable guys like you could really make a difference.

so, i'm glad you're taking this course and trying to change the outcome of this game. keep up the good work. i'm looking forward on your progress and findings.

----------


## FGF11

> hey FGF11, nice work. we have some members here who somehow have a deeper background about biology and chemistry but for the first time i have a feeling that with you we have a real scientist here finally. you seem to know how stuff works and also have access to tools and equipment to test different theories. that's fantastic. i really think you could be onto something and even if some your thoughts turn out as wrong, i feel you can help greatly to understand the AGA mechanism and maybe even find some solution to it.
> i strongly believe that if more members like you would take things into their own hands, we would already have a solution or at least better treatment options. 
> it would highly suggest that you let someone set up a site or blog for you where you can summarize and share your findings. an open science community would definitely accelerate the process in finding treatments for AGA. i'm not at all relying on the hairloss researchers like cotsarelis and others. they might have good knowledge and experience but they are not eager enough to really solve problems. they are tinkering around in their labs for decades without significant progress. an open science with knowledgeable guys like you could really make a difference.
> 
> so, i'm glad you're taking this course and trying to change the outcome of this game. keep up the good work. i'm looking forward on your progress and findings.


 
Yea, either tomorrow or 20 years from now. I will solve this shit. Glad I didn't raise your BS detector. HAHA.

----------


## Swooping

> Okay, I explain a little more about castration: 
> 
> Look, What is the role of castration? You take the balls out. Right? no testosterone anymore. So basically no DHT anymore. And no further miniaturization right. please read my writing as intelligently as possible. Miniaturization is DHT dependent. So you basically stop hair loss. No more DHT and testosterone binds the AR, so it can't get into the nucleus and drive miniaturization. But you're not inhibiting cytoplasmic AR, which, binds Beta-catenin either in presence of DHT or absence of DHt. Castration do not reduce AR expression levels. So, you won't see regrowth. Beta-catenin can't act in presence of AR. The binding of AR and beta-catenin is no completely DHT dependent. It's explained in the link I sent you.


 So per your hypothesis you argue that AR expression increases over time. On what evidence do you base this? If this does happen then why is a compound like finasteride generally effective over many years? If AR expression would increase over time finasteride highly likely wouldn't provide such a long lasting effect. I don't see why a compound like finasteride would suddenly stop the increased AR expression from happening, I don't see in the first place why AR expression would get higher over time. Perhaps I'm missing something here though? 

Secondly what experiment(s) led you to the notion that AR expression competes with b-catenin and can even render it inactive, can you give more information about these experiments? Or is this a known fact, if so could you pass me the literature? 

Thanks. There is nothing wrong btw with hypothesizing, researching etc. It's only a good thing imo. It does however become stupid when one makes claims and then doesn't show up. We have seen enough of that stuff. Thanks.

----------


## Swooping

> FGF11 - I appreciate all the work you are doing. Can you please address my question though. Why would AR issues cause balding in a pattern? Why would minoxidil be the BEST growth stimulator if the problem was purely AR? It doesn't add up. Dermarolling + Minoxidil are far better growth stimulators than Finasteride will ever be.


 This might be of interest to you;

----------


## FGF11

> So per your hypothesis you argue that AR expression increases over time. On what evidence do you base this? If this does happen then why is a compound like finasteride generally effective over many years? If AR expression would increase over time finasteride highly likely wouldn't provide such a long lasting effect. I don't see why a compound like finasteride would suddenly stop the increased AR expression from happening, I don't see in the first place why AR expression would get higher over time. Perhaps I'm missing something here though? 
> 
> Secondly what experiment(s) led you to the notion that AR expression competes with b-catenin and can even render it inactive, can you give more information about these experiments? Or is this a known fact, if so could you pass me the literature? 
> 
> Thanks. There is nothing wrong btw with hypothesizing, researching etc. It's only a good thing imo. It does however become stupid when one makes claims and then doesn't show up. We have seen enough of that stuff. Thanks.


 
Yes, AR expression increases overtime as hair follicle miniaturizes. Finasteride stops hair follicle miniaturization. Increased AR expression is the hallmark of male hair loss. Expression of the AR has also been found to be increased in balding scalp. 


Finasteride is effective, as it stops gradual increase in AR expression, by stopping AGA from progressing and AR from getting activated, keeping AR levels normal. Increased AR expression is an AR dependent mechanisms. As AR is the driving force of AGA. So by catching hair loss early by taking finasteride, you stop gradual increase in the levels of AR. I hope this answers your first question. I leave the literature search on yourself.

As for the second question:

^ this is in AGA keratinocytes, levels of total beta-catenin has not changed, but levels of cytoplasmic beta-catenin in presence of DHT is negligible. This is done in AGA keratinocytes.

^ this is again in AGA keratinocytes. 
First you can see that in presence and absence of DHT, AR receptor binds GSK-3beta ( a know regulator of beta-catenin).



read the figure, and take notice of the way beta-catenin and AR receptor acts differently in Keratinocytes of patients with AGA and normal keratinocytes. In normal patients, in presence of DHT both AR and Beta-catenin are in the cell nucleus. While, in patients with AGA, Beta-catenin can't get into nucleus. However, in presence of Wnt3A, the reverse happens. Note, that all the studies I am bringing here have been done in AGA compared with non-AGA (mostly in keratinocytes).

However, it is a completely known fact that AR and Beta-catenin antagonize in epithelial cells of mice. 
[http://www.nature.com/jid/journal/v1...2015242a.html]

There about much more articles out there. Please read them carefully and if you are still not convinced let know.

----------


## FGF11

> So per your hypothesis you argue that AR expression increases over time. On what evidence do you base this? If this does happen then why is a compound like finasteride generally effective over many years? If AR expression would increase over time finasteride highly likely wouldn't provide such a long lasting effect. I don't see why a compound like finasteride would suddenly stop the increased AR expression from happening, I don't see in the first place why AR expression would get higher over time. Perhaps I'm missing something here though? 
> 
> Secondly what experiment(s) led you to the notion that AR expression competes with b-catenin and can even render it inactive, can you give more information about these experiments? Or is this a known fact, if so could you pass me the literature? 
> 
> Thanks. There is nothing wrong btw with hypothesizing, researching etc. It's only a good thing imo. It does however become stupid when one makes claims and then doesn't show up. We have seen enough of that stuff. Thanks.


 
Tnx, the  moment I feel that I am wrong, I have no shame of stating it. Also, I listened to Dr. Christiano interview which was posted here, you can see that they can't go ahead and test their compounds, because it is hard to do so. People should know that science is really hard and take time. Even for some one as recognized as her, it's incredibly hard to convince pharma to come and fund something that MIGHT have some effect. lol, let alone me. haha. So that's why I have decided to take things in my own hand. Also I'm up to some other stuff hair wise, that I'm not interested bringing them here for some reasons. She is a nice person though.

----------


## FGF11

ALSO, I would like you to notice the effect of LiCl, on beta catenin in presence of DHT, or maybe increased AR. I'm actually trying to be very careful, as not rising any false hope, all I'm saying is that this thing is much more effective (at least) than anything in the market, and the only reason it's not here, is because it is EXTREMELY expensive and EXTREMELY hard to deliver.

----------


## FGF11

Search this in google: "beta catenin androgen receptor interaction".  I'm also going to not have access to here for a month or more.

----------


## FGF11

> Search this in google: "beta catenin androgen receptor interaction".  I'm also going to not have access to here for a month or more.


 HAIRLOSS JUST SUCKS, I KNOW IT"S CHILDISH BUT I WISH EVERYONE COULD UNITE. There is no other way around this.

----------


## Swooping

> Yes, AR expression increases overtime as hair follicle miniaturizes. Finasteride stops hair follicle miniaturization. Increased AR expression is the hallmark of male hair loss. Expression of the AR has also been found to be increased in balding scalp. 
> 
> 
> Finasteride is effective, as it stops gradual increase in AR expression, by stopping AGA from progressing and AR from getting activated, keeping AR levels normal. Increased AR expression is an AR dependent mechanisms. As AR is the driving force of AGA. So by catching hair loss early by taking finasteride, you stop gradual increase in the levels of AR. I hope this answers your first question. I leave the literature search on yourself.


 Well I have read pretty much every study, so I know that there is evidence of higher AR expression in balding scalp (vertex, frontal) versus occipital. However to my knowledge, there is zero evidence that shows that AR expression increases over time during miniaturization, The studies that have been made show simply a static measurement where they take tissue from the scalp in a person and then they compare tissue from occipital to vertex or the front. I have never seen a study that suggests what you say, including the above. For that to happen they would need to follow-up subjects several years later from the first measurement. I would be very surprised if such a study exists.

I'll go over that other information one time later, quite busy at the moment. Will be following you though. Thanks anyway and I wish you good luck.

----------


## youngin

> Well I have read pretty much every study, so I know that there is evidence of higher AR expression in balding scalp (vertex, frontal) versus occipital. However to my knowledge, there is zero evidence that shows that AR expression increases over time during miniaturization, The studies that have been made show simply a static measurement where they take tissue from the scalp in a person and then they compare tissue from occipital to vertex or the front. I have never seen a study that suggests what you say, including the above. For that to happen they would need to follow-up subjects several years later from the first measurement. I would be very surprised if such a study exists.
> 
> I'll go over that other information one time later, quite busy at the moment. Will be following you though. Thanks anyway and I wish you good luck.


 The studies I see on AR expression or 5aR are always bald vs non-bald DP cells. Has no one investigated these expressions PRE balding? Just because its increased after balding doesn't make it the cause. Maybe external factors cause the change of expression.

If we hypothesize that AR expression is part of the problem that's fine, but why throw all of the other highly studied aspects out of the window? Has anyone felt the scalp of a NW7? I am NW6 and I can tell you that the vertex (earliest balding) of my scalp looks and feels like scar tissue. Do you think you can grow hair through scar tissue just with AR antagonists of sorts? Highly unlikely. My stance is that THIS is why dermarolling and minoxidil work.

By all means lets all figure this out but focusing on one single aspect is not doing anything new, especially with huge amounts of evidence based around immune issues and surrounding tissue.

----------


## Swooping

> The studies I see on AR expression or 5aR are always bald vs non-bald DP cells. Has no one investigated these expressions PRE balding? Just because its increased after balding doesn't make it the cause. Maybe external factors cause the change of expression.
> 
> If we hypothesize that AR expression is part of the problem that's fine, but why throw all of the other highly studied aspects out of the window? Has anyone felt the scalp of a NW7? I am NW6 and I can tell you that the vertex (earliest balding) of my scalp looks and feels like scar tissue. Do you think you can grow hair through scar tissue just with AR antagonists of sorts? Highly unlikely. My stance is that THIS is why dermarolling and minoxidil work.
> 
> By all means lets all figure this out but focusing on one single aspect is not doing anything new, especially with huge amounts of evidence based around immune issues and surrounding tissue.


 Well that's what I'm saying. FGF11 says that androgen receptor expression increases over time and that this results in miniaturization due to eventually AR competing with b-catenin. However like you mention evidence has never been shown that AR expression increases over time in balding scalp. What has been shown however in one measurement is that AR expression is higher in balding scalp in *comparison* to non-balding scalp. To my knowledge measurements have been never made pre-balding and after a while of balding to measure a possible increase of AR expression.

I'm not saying it's not possible,  But evidence hasn't been shown yet for increase of AR expression over time in the balding scalp. At least not that I know? Maybe FGF11 does.

Also remember I don't hypothesize that AR expression is the problem, FGF11 does. I'm more in the camp of cell cycle arrest or senescence that relies on indicative evidence shown in papers by various researchers. That would be my line of thinking. Pure hypothetical thinking of me though, I don't make claims or project it as the truth.

You make a interesting point about* fibrosis*. Before I didn't think it was such problem in AGA. Simply because fibrosis is literally scarring and too much scarring will simply destroy the hair follicle, just as we see in cicatrial alopecia. Cicatrial (scarring) alopecia consists basically of fibrosis that leads to complete destruction of the hair follicle that is seen as irreversible. Until, one day maybe  we are able to induce morphogenesis of hair follicles that could potentially fix the problem in something like cicatrial alopecia.

Guess I was wrong and you make a very good point, I do think fibrosis plays a role in (advanced) AGA. When we look at a study of Domyati(1.) for example;




> In the frontal bald area of AGA, perifollicular fibrosis consisting of loose concentric layers of collagen was generally absent in 16 cases (40%) or mild in 14 cases (35%) in young age with mild AGA (Figure 2c). It was more marked,* even with destruction of follicular structures, in the old age group with advanced AGA.* The arrector pili muscle may be retained (Figure 2d). Perifollicular fibrosis showed highly significant correlation with both age of the patients (r = 0.78, P < 0.001) and correlated significantly with the severity of baldness (r = 0.46, P = 0.003). It showed significant inverse correlation with perifollicular inflammation (r = )0.31, P = 0.048). In normal controls, neither inflammatory infiltrate, apart from sparse perivascular infiltrate in a few biopsies, nor perifollicular fibrosis was observed in all studied specimens.


 


> In the frontal (bald) area of AGA, perifollicular inflammatory infiltrate was observed in the majority of cases (90%). Meanwhile, no fibrosis was observed in 40% and only 10% showed marked fibrosis and complete destruction of hair follicles in the old age group with advanced AGA. These results are close to those observed by El-Domyati  who reported inflammatory reaction in female subjects with AGA with destruction of follicular structure and replacement by fibrous tracts in severe cases. Meanwhile, Abell26 reported an inflammatory reaction in 75% of balding patients, *focal fibrosis in 25%,** and destruction of follicular structures in 5%.*


 


> Kligman25 demonstrated that perifollicular fibrosis was due to deposition of concentric layers of perifollicular collagen. The perifollicular fibrosis was evidenced by degranulation of follicular adventitial mast cells as well as enhanced collagen production by neighboring fibroblasts which resulted in 2- to 2.5-fold enlargement of the follicular dermal sheath.27


 (The degranulation of mast cells should explain the PGD2 fanboys one possible explanation for increased PGD2 in scalp by the way. The largest amount of PGD2 is found in mast cells in the human body)

So I do believe fibrosis can become a problem and in some advanced cases even in AGA can cause destruction of the hair follicle, which would make AGA* irreversible* in some (very advanced) cases. Only creation of new hair follicles would help in this case. 

That being said out of all the studies I would personally place my bet that AGA is simply premature senescence. Everything that happens correlates with senescence imo, including the inflammatory aspect of AGA. I hope this evidence towards senescence is completely wrong though, cause that would be f*cked up.

*One thing is for sure imo, if you can make sure you take preventative measures. You might regret it later if you don't.*




1. http://www.ncbi.nlm.nih.gov/pubmed/19527330)

----------


## youngin

Just to be clear I wasn't directing my last post at you Swoop, I was just piggy backing your quote. I agree with what you said. I am sure that cellular senescence is definitely involved, but this is a chain of events. Something like (CAUSE) -> Androgens -> Inflammation -> Fibrosis.. with the cause being still unknown or multi-factor. I think that calcium issues fit in this chain somewhere as well (Note BMP's affect on hair growth). I'll never forget reading the report about the doctor finding knitted calcification through the veins in the head of a bald cadaver. When you are as bald as me you can feel and see differences in the scalp.

----------


## youngin

A relevant hint about minoxidil:



> Since collagen is the major product of fibroblast activity and lysyl hydroxylase catalyzes a crucial reaction in collagen biosynthesis, the combined effects of *minoxidil offer the potential for its use as an antifibrotic agent. Thus, minoxidil may prove to be beneficial in treating skin conditions associated with collagen accumulation.*


 http://www.ncbi.nlm.nih.gov/pubmed/2826267

This is the strongest reasoning of why minoxidil works. It can reverse some fibrosis. Yet everyone tries to force some line of reasoning to make it align with androgen activity.

----------


## FGF11

> Well I have read pretty much every study, so I know that there is evidence of higher AR expression in balding scalp (vertex, frontal) versus occipital. However to my knowledge, there is zero evidence that shows that AR expression increases over time during miniaturization, The studies that have been made show simply a static measurement where they take tissue from the scalp in a person and then they compare tissue from occipital to vertex or the front. I have never seen a study that suggests what you say, including the above. For that to happen they would need to follow-up subjects several years later from the first measurement. I would be very surprised if such a study exists
> 
> I'll go over that other information one time later, quite busy at the moment. Will be following you though. Thanks anyway and I wish you good luck.


 
Tnx, yes. No longitudinal studies have been done on AR expression during progression of AGA. However, studies haven been done on AR expression in presence of DHT. DHT induce AR expression. This basically equals a longitudinal study, and shows that if DHT not stopped, AR levels will increase.

----------


## Ulti1

> A relevant hint about minoxidil:
> 
> http://www.ncbi.nlm.nih.gov/pubmed/2826267
> 
> This is the strongest reasoning of why minoxidil works. It can reverse some fibrosis. Yet everyone tries to force some line of reasoning to make it align with androgen activity.


 Yeah I think fibrosis and calcium build up is a big problem.  My scalp visually looks different and it's not the sebum.  I had a crap ton of oil and sebum before I started losing hair and my scalp looked pearly white and healthy, it never flaked or caused build up.. 
Now my scalp looks like it's caked on with calcium or some shit.. I don't think it helps that my nails are so thick and made out of steel. I think I have too much calcium.  No more milk for this guy.

----------


## ShookOnes

pretty sure tb 500 is the only thing legit besides fin minox atm.

----------


## trunks

> A relevant hint about minoxidil:
> 
> http://www.ncbi.nlm.nih.gov/pubmed/2826267
> 
> This is the strongest reasoning of why minoxidil works. It can reverse some fibrosis. Yet everyone tries to force some line of reasoning to make it align with androgen activity.


 Really interesting

Regarding another possible Minoxidil effect on AGA:
Minoxidil may suppress androgen receptor-related functions




> We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a Kd value of 2.6 μM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases


 Maybe this feature makes Minoxidil effectibe on early AGA?

----------


## UNBEAT

I have oily scalp too, with to much sebum that creates flakes and hair loss with plugs. Do you think that minoxidil can help

----------


## Swooping

> Just to be clear I wasn't directing my last post at you Swoop, I was just piggy backing your quote. I agree with what you said. I am sure that cellular senescence is definitely involved, but this is a chain of events. Something like (CAUSE) -> Androgens -> Inflammation -> Fibrosis.. with the cause being still unknown or multi-factor. I think that calcium issues fit in this chain somewhere as well (Note BMP's affect on hair growth). I'll never forget reading the report about the doctor finding knitted calcification through the veins in the head of a bald cadaver. When you are as bald as me you can feel and see differences in the scalp.


 I get what you mean although I think everything starts with Androgens > AR. So it starts from the microenvironment imo. The whole process is definitely intriguing though.

Do you have some literature to read about the stuff you mention? I would be interested, thanks.

----------


## UNBEAT

Any news from fgf11?

----------


## youngin

> I get what you mean although I think everything starts with Androgens > AR. So it starts from the microenvironment imo. The whole process is definitely intriguing though.
> 
> Do you have some literature to read about the stuff you mention? I would be interested, thanks.


 Here is the article I was talking about at the end of my post: http://jama.jamanetwork.com/article....ticleid=256511

This guy has a similar idea (http://www.evolutionary.org/forums/a...pic-28623.html) though I don't agree with everything said. He even quotes some articles that correlate steroid usage (higher test) to calcification.

----------


## youngin

Swoop,

Look at this interesting study as well: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639964/ Mechanical stress could be how AGA starts.

----------


## Chemical

> Swoop,
> 
> Look at this interesting study as well: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639964/ Mechanical stress could be how AGA starts.


 I've read that study and thought it was quite interesting so I'm going to add something to the discussion. 

I think you should be careful of confirmation bias because you'll only find what you want to believe, you might even turn a blind eye to some facts so I'd wholeheartedly suggest keeping an open mind. I say this from personal experience. 

Fir clarification, the study does suggest "mechanical stress" in the title but they dont actually mean that, heres  what they say in their results/discussion:




> The involuntary tonic *contraction of occipitofrontalis muscle* is related to *psychological stress conditions*,[23] facial expression,[24] the maintenance of visual field,[19] and an aponeurotic tension model of human craniofacial growth,[25] so the galea aponeurotica supports a continuous stress which is transmitted to ECM and cells of each tissue, dermal papilla, and dermal sheath cells included. The *deformation energy does not cause apparent damage to scalp skin, but its interplay with androgens could be fatal in organ remodeling of hair follicles.* This androgen-mediated molecular response to mechanical stimulation can play the *anabolic role instead of biological virilization role*, as it has been extensively studied in tissues whose function is closely linked to the physical force support.[26] Furthermore, it has been reported that *TGFβ-1 increases the expression of Hic-5 in hypertrophic scars fibroblasts[27] and it potentiates AR transactivity in balding dermal papilla cells[28] by autocrine loop* [Figure 3]. Hence, the long-lasting cyclic strain would cause a slow, chronic, and progressive environmental adaptation process in balding hair follicles since puberty.


 They've said here that the mechanical stresses are a combination of muscular tension from stress, facial expressions, and the eye movements. what? Thats a bizarre finding. However, thats not the conclusion!

They propose the idea that this muscular stress causes an increase in anabolism. Like when you train your biceps, AR expression gets increased and local IGF-1R gets upregulated as a result of the environmental stressors. Thats why working out makes your muscles bigger.

So this increase in AR activity increases TGF-Beta1 (via DPC), which then increases Hic-5, and Hic-5 potentiates AR activity in DPC leading to a closed positive feedback. According to their theory.

This is quite interesting because TGF-Beta is known to inhibit hair growth in a paracrine manner, but it also causes fibrosis when overexpressed - like you've been going on about! 




> In many diseases, *excessive TGF-beta* contributes to a pathologic excess of tissue fibrosis that compromises normal organ function, a topic that has been the subject of numerous reviews [1-3]


 Furthermore:




> *Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.*
> 
> R1881 stimulated the growth of KCs by 41% when cocultured with beard DPCs (Fig. 3A, lane 1 vs. 2). In contrast, R1881 decreased the growth of KCs by 50% in the coculture with DPCs from AGA (Fig. 3A, lane 3 vs. 4). R1881 showed no significant effect on the growth of KCs cocultured with either nonbald frontal or occipital DPCs (Fig. 3A, lane 5 vs. 6 and lane 7 vs. 8).


 I'd recommend reading the full pdf, its got some revealing insights. 

R1881 is an AR agonist. When the balding hair follicles were co-cultured with keratinocytes, they had reduced proliferation. In contrast, beard hair follicles *stimulated* KC growth (via paracrine IGF-1). The balding hair follicles secreted TGF-Beta1 when stimulated with the AR agonist.




> The *concentration of total TGF-β1* in the conditioned medium treated with 109 M R1881 *was increased by 2.68-fold* compared with the control (Fig. 5, lanes 1 and 2). *Anti-androgen CPA* at the concentration of 106 M completely *diminished this increase*, demonstrating that the androgen-AR system is involved in the induction of TGF-β1 (Fig. 5, lane 3). Moreover, the concentration of active TGF-β1 was 174.1 pg/ml in the medium treated with 109 M R1881, whereas it was 12.9 pg/ml in the medium treated with ethanol (Fig. 5, lanes 4 and 5). Likewise, this induction of active TGF-β1 was reversed by 106M CPA (Fig. 5, lane 6). From these results, the TGF-β1 activity is regulated by androgens through both its production and activation. When DPCs from the nonbald frontal scalp were cocultured with KCs, 109 M R1881 did not show any significant effect on the concentration of total and active TGF-β1 in the conditioned medium (Fig. 5, lanes 710).


 So you can see that the AR is the main mediator of this cascading chain. By blocking AR you can prevent the TGF-Beta1 induced fibrosis. Skin is not a fixed organ. Its constantly renewing, just like hair. The hair doesnt grow at the tips, it grows at the root, it starts bottom. Skin does the same. If TGF-Beta stops signalling to nearby DPC/KC and fibroblasts then the skin can turnover the fibrosis as it sheds the layers. But if TGF-Beta is present then you'll constantly have fibrosis present. Your theory is spot on, but the cause is AR like FGF11 and swoop have been talking about. 

I hope this has shed some light on this topic.

----------


## youngin

I like the civil conversation we are having and exchanging ideas. I don't have much time to respond right now but I have to say Chemical I don't think you can do anything with AR and reverse fibrosis and calcification of surrounding tissue. It's very likely AR is part of the cause but once fibrosis sets in I believe you are stuck without minoxidil which basically removes it to an extent, and manual wounding. This is exactly why castration doesn't regrow all hair.

----------


## Swooping

Thank guys very interesting things mentioned here.

@youngin, thanks will be going over that literature soon and will respond after  :Smile: .

----------


## youngin

I think this study is very clearly explained.




> They've said here that the mechanical stresses are a combination of muscular tension from stress, facial expressions, and the eye movements. what? Thats a bizarre finding. However, thats not the conclusion!


 This is not bizarre at all. I'm not sure if you really understood what they were pointing out. Psychological stressors can become physical, like stress causing jaw tension, brow movement, etc. These use muscles that move and tighten the galea, which then causes mechanical stress on the follicle cells causing a cascade of Hic-5 -> AR -> inflammation -> fibrosis. This is not unusual as many cells in our body respond to mechanical stress (see bones).




> So you can see that the AR is the main mediator of this cascading chain. By blocking AR you can prevent the TGF-Beta1 induced fibrosis. Skin is not a fixed organ. Its constantly renewing, just like hair. The hair doesnt grow at the tips, it grows at the root, it starts bottom. Skin does the same. If TGF-Beta stops signalling to nearby DPC/KC and fibroblasts then the skin can turnover the fibrosis as it sheds the layers. But if TGF-Beta is present then you'll constantly have fibrosis present. Your theory is spot on, but the cause is AR like FGF11 and swoop have been talking about.


 I have to disagree. When I speak about cause I do not mean a single link in a chain, I am speaking about ROOT cause. In this case AR is not the root cause, mechanical stress would be if such a hypothesis were correct. If this could be definitively proven (I'm not saying it is) then would you treat AR as the cause or the tension problem?? It's interesting that the Botox study gets ignored even though the author has been open about it as well.
http://journals.lww.com/plasreconsur...ulinum.79.aspx

----------


## Chemical

> I think this study is very clearly explained.
> 
> This is not bizarre at all. I'm not sure if you really understood what they were pointing out. Psychological stressors can become physical, like stress causing jaw tension, brow movement, etc. These use muscles that move and tighten the galea, which then causes mechanical stress on the follicle cells causing a cascade of Hic-5 -> AR -> inflammation -> fibrosis. This is not unusual as many cells in our body respond to mechanical stress (see bones).


 I didnt explain myself properly, sorry. They mentioned physiological factors that everyone is likely to experience at some point in their life. The kinds of stress they are talking about dont seem to be extreme enough like working out or gravity (bone mechanosensitivity). This involuntary natural movement of muscles without any form of resistance shouldnt warrant an increase in anabolism. In the case of bone, normal muscular movements and activity does not automatically lead to osteoblastogenesis, theres a cellular threshold. Thats why people in space use resistance training to keep mineral bone density high. The same principles apply to muscle. You can't cause muscle to grow by just moving it without resistance. This is whats baffling me.

They were specifically referring to the muscle in the forehead region: 




> The involuntary tonic contraction of occipitofrontalis muscle


 The hairs themselves are designed to withstand tugging and mechanical pulling forces, but excessive traction can lead to hairloss. They're suggesting the occipitofrontalis muscle is increasing local androgen sensitivity. That's something I dont understand. Hic-5 activation is controlled by forces action on the cytoskeleton. DHT is known to increase the expansion of the skull so maybe that triggers Hic-5 indirectly leading to increased anabolism?. 




> Interestingly, a triggering stimulus that can alter the inactive standby status of Hic-5 is the deformation of the cytoskeleton by physical forces;[15,16] therefore, mechanical stimulation can promote overexpression of molecular signals implicated in AGA pathogenesis.


 Furthermore:




> Regardless the pattern or degree of severity, *AGA is always limited to the skin overlying the galea aponeurotica*. This is a thin and relatively inelastic tendon-like tissue sheet that communicates the frontal and occipital bellies of occipitofrontalis muscle.[17] Balding scalp skin is firmly bounded to galea by fibrous rigid subcutaneous layer, so elastic deformation affecting the galea is shared by the three upper layers as a structural unit[18] [Figure 1], whereas the remaining scalp skin freely slides over deeper layer, with low strain transmission to hair follicles and unaffected by AGA.


 The pattern that AGA manifests is linked to the region they are talking about. Their model/simulation isnt too conclusive but I think  its a valid hypothesis.

Addressing your point about fibrosis:




> I don't think you can do anything with AR and reverse fibrosis and calcification of surrounding tissue. It's very likely AR is part of the cause but once fibrosis sets in I believe you are stuck without minoxidil which basically removes it to an extent, and manual wounding. This is exactly why castration doesn't regrow all hair.


 It appears fibrosis isnt permanent as one might expect. Fibrosis can be reduced, but it doesnt happen with a magic drug. Minoxidil actually cant reverse fibrosis the way you think it does. It doesnt break down fibrotic tissue. But in the presence of minoxidil, fibroblasts cannot create fibrotic tissue properly. Look at this study:




> Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: implications for collagen cross-linking and treatment of fibrosis.
> 
> Abstract
> Collagen deposits in fibrotic lesions often display elevated levels of hydroxyallysine (pyridinoline) cross-links. The relation between the occurrence of *pyridinoline cross-links and the irreversibility of fibrosis suggests that these cross-links contribute to the aberrant accumulation of collagen.* Based on *its inhibitory effect on lysyl hydroxylase activity minoxidil has been postulated to possess anti-fibrotic properties by limiting the hydroxylysine supply for hydroxyallysine cross-linking.* However, to interfere with hydroxyallysine cross-linking specifically lysyl hydroxylation of the collagen telopeptide should be inhibited, a reaction predominantly catalysed by lysyl hydroxylase (LH) 2b. In this study, we demonstrate that minoxidil treatment of cultured fibroblasts reduces LH1>>LH2b>LH3 mRNA levels dose-and time-dependently, but *has essentially no effect on the total number of pyridinoline cross-links in the collagen matrix.* *Still the collagen produced in the presence of minoxidil displays some remarkable features: hydroxylation of triple helical lysine residues is reduced to 50% and lysylpyridinoline cross-linking is increased at the expense of hydroxylysylpyridinoline cross-linking*. These observations can be explained by our finding that LH1 mRNA levels are the most sensitive to minoxidil treatment, corroborating that LH1 has a preference for triple helical lysine residues as substrate. In addition, the non-proportional increase in cross-links (20-fold) with respect to the decrease in lysyl hydroxylation state of the triple helix (2-fold) even suggests that LH1 preferentially hydroxylates triple helical lysine residues at the cross-link positions. We conclude that *minoxidil is unlikely to serve as an anti-fibroticum, but confers features to the collagen matrix,* which provide insight into the substrate specificity of LH1.


 *This study* also confirms minoxidils rate limiting effect on fibrosis generation.

The fibrotic chains/links are heavily blunted due to minoxidil, somehow the fibroblasts are unable to create *new* fibrotic deposits in the ECM. The existing fibrosis is not affected. 

However, according to this study, fibrosis isnt permanent and is reversible:




> A Peptide Derived from Endostatin Ameliorates Organ Fibrosis
> 
> To assess whether endostatin peptides could reverse fibrosis that was already present, we injected E4 into human skin 2 days after a single TGF-β administration, when dermal thickness was already evident (fig. S3, A and B; P = 0.045, TGF-β versus vehicle). Similar to human skin cotreated with E4 and TGF-β, delayed E4 administration also significantly ameliorated TGF-βinduced dermal fibrosis (Fig. 2, E and F). Our findings indicate that the C-terminal peptide of endostatin can prevent the development and progression of fibrosis and can also reverse TGF-βinduced fibrosis in human skin.
> 
> The N-terminal peptide of endostatin has been reported to ameliorate peritoneal sclerosis by reducing expression of TGF-β and α-SMA (31). Neutralization of endostatin exaggerated tissue remodeling and interstitial fibrosis with increased tissue collagen and MMP-2 and MMP-9 activities in a rat myocardial infarction model (34). These reports suggest that endostatin might interact with some profibrotic factors in fibroproliferative circumstances. In our experiments, E3 and E4 reduced dermal thickness of mouse and human skin treated with TGF-β and also inhibited bleomycin-induced skin and lung fibrosis. This suggests that the antifibrotic effect of the endostatin C-terminal peptide may be due, in part, to its blockade of TGF-β activity.


 I would encourage you read to read the full pdf. 

Inhibition of TGF-Beta causes the reversal of fibrosis. Which means fibrosis is only present so long as an agent is promoting it. Once you remove the stimulus, it cant sustain itself. AR -> TGF-Beta. You silence AR and you prevent the rise in TGF-Beta. A reduction in TGF-Beta as the study has pointed out, leads to a gradual decrease in fibrotic tissue in ECM.




> I have to disagree. When I speak about cause I do not mean a single link in a chain, I am speaking about ROOT cause. In this case AR is not the root cause, mechanical stress would be if such a hypothesis were correct. If this could be definitively proven (I'm not saying it is) then would you treat AR as the cause or the tension problem?? It's interesting that the Botox study gets ignored even though the author has been open about it as well.
> http://journals.lww.com/plasreconsur...ulinum.79.aspx


 That botox study is a good find, and once again it ties in with AR as per the authors conclusions. Botox increases HIF-1/VEGF and I've covered the hair growth promotive effects of this pathway over in my thread.




> Mechanistically, the scalp behaves like a drum skin with tensioning muscles around the periphery. These muscle groupsthe frontalis, occipitalis, and periauricular muscles and to a minor degree the temporaliscan create a tight scalp when chronically active. Because the blood supply to the scalp enters through the periphery, a reduction in blood flow would be most apparent at the distal ends of the vessels, specifically, the vertex and frontal peaks. Areas of the scalp with sparse hair growth have been shown to be relatively hypoxic, have slow capillary refill, and to have high levels of dihydrotestosterone.4Conceptually, Botox loosens the scalp, reducing pressure on the perforating vasculature, thereby increasing blood flow and oxygen concentration. The enzymatic conversion of testosterone to dihydrotestosterone is oxygen dependent. In low-oxygen environments, the conversion of testosterone to dihydrotestosterone is favored; whereas in high-oxygen environments, more testosterone is converted to estradiol.4


 Is it mere coincidence that the AR is implicated in nearly every study relating to hairloss (both directly and indirectly)? I'm a rational person, I believe things that have correlation and justifiable/rational causative mechanisms. 

The elusive *root cause* that you are referring to is the genetic component. Unless you can use epigenetics or gene targeting, its a hopeless endeavor. AR is the biggest factor that mediates the genetic predisposition to AGA. If you get rid of the strongest link in the chain, the rest of the chain becomes useless, this is why targeting the AR pathway is so efficient. By taking down one pathway you automatically cancel out the rest, thats a much easier task than trying to shutdown genes(?). I understand if you disagree, but what do you reckon the root cause might be besides the AR? The mechanical stress aggravates AR induced hairloss, this is quite clear, so that theory is out the window. The only other theory people have postulated are PGD2 and autoimmunity which I'm not sold on.

----------


## youngin

> I didnt explain myself properly, sorry. They mentioned physiological factors that everyone is likely to experience at some point in their life. The kinds of stress they are talking about dont seem to be extreme enough like working out or gravity (bone mechanosensitivity). This involuntary natural movement of muscles without any form of resistance shouldnt warrant an increase in anabolism.


 This is not quite true. You do not have to do resistance training to grow muscle. This happens quite naturally for a man going into his teenage years. Also, you cant say there is no resistance in these forehead muscle movement either. Muscle and skull growth changed quite obviously through male puberty.



> In the case of bone, normal muscular movements and activity does not automatically lead to osteoblastogenesis, theres a cellular threshold. Thats why people in space use resistance training to keep mineral bone density high. The same principles apply to muscle. You can't cause muscle to grow by just moving it without resistance. This is whats baffling me.


 Actually the point I was making was not about osteoblastogensis, it was about cellular structure changes and signalling because of mechanical stress. As seen in the book "The Body Electric" bones actually even emit different electrical signaling when under tension.



> The hairs themselves are designed to withstand tugging and mechanical pulling forces, but excessive traction can lead to hairloss. They're suggesting the occipitofrontalis muscle is increasing local androgen sensitivity. That's something I dont understand. Hic-5 activation is controlled by forces action on the cytoskeleton. DHT is known to increase the expansion of the skull so maybe that triggers Hic-5 indirectly leading to increased anabolism?.


 You may need to re-read the study again to understand what they are saying about mechanical stress. I do not see anything being linked directly to the occipital muscles besides that being the source of force.



> It appears fibrosis isnt permanent as one might expect. Fibrosis can be reduced, but it doesnt happen with a magic drug. Minoxidil actually cant reverse fibrosis the way you think it does. It doesnt break down fibrotic tissue. But in the presence of minoxidil, fibroblasts cannot create fibrotic tissue properly. Look at this study: The fibrotic chains/links are heavily blunted due to minoxidil, somehow the fibroblasts are unable to create *new* fibrotic deposits in the ECM. The existing fibrosis is not affected.


 Yes. I mistakenly said "reverses" thought I did not mean it literally. It blunts collagen formation and probably calcification while your cells recycle as per usual. The dermarolling probably speeds this up with wounding and prompting repair of the skin cells, while minoxidil is stopping the fibrosis from happening during repair.



> That botox study is a good find, and once again it ties in with AR as per the authors conclusions. Botox increases HIF-1/VEGF and I've covered the hair growth promotive effects of this pathway over in my thread.


 I think this is another stretch. Science is very aware of what VEGF is used for and it does not have a strong link to AR. It has a strong link to vascular modeling. This is not just a side function, this is the MAIN function. We can't make these pieces of the puzzle fit to our own agenda. 



> Is it mere coincidence that the AR is implicated in nearly every study relating to hairloss (both directly and indirectly)? I'm a rational person, I believe things that have correlation and justifiable/rational causative mechanisms.


 It's not a coincidence, it definitely is a link in the chain. MOST studies MUST agree AGA is caused by AR from the outset and this is the focus, they do not focus on other pathways. So its not really a coincidence if you are targeting a specific pathway.



> The elusive *root cause* that you are referring to is the genetic component. Unless you can use epigenetics or gene targeting, its a hopeless endeavor.


 No one has discovered the root cause, thats why we have these hypothesis. PGD2 and immunity are probably downstream of androgen activity in the chain. It maybe multi-factor epigenetic. The monozygotic twin studies show that it IS a factor.

----------


## Chemical

> This is not quite true. You do not have to do resistance training to grow muscle. This happens quite naturally for a man going into his teenage years. Also, you cant say there is no resistance in these forehead muscle movement either. Muscle and skull growth changed quite obviously through male puberty.


 The changes that happen during puberty are a result of pubertal HGH/IGF-1 spikes. Although this is deviating considerably from the point I was making about force/stress induced anabolism. I think the resistance from tendons and skin is not enough to promote an anabolic reaction, this is my point.




> Actually the point I was making was not about osteoblastogensis, it was about cellular structure changes and signalling because of mechanical stress. As seen in the book "The Body Electric" bones actually even emit different electrical signaling when under tension.


 Structural changes as a result of environental stresses is a general statement. We are talking about an increase in anabolism (AR upregulation is an anabolic reaction), hence my reference to osteoblastogenesis. Under compressional forces bone tries to increase osteoblastogenesis - which requires calcium/phosphate. In the case of deficiency in calcium/phosphate/D3, bone deformation will occur. What I'm trying to say is that the body favours anabolism when counteracting environmental stressors it cant handle. I guess it is possible for AGA predisposed frontal hair to react to environmental stresses and upregulate AR.




> You may need to re-read the study again to understand what they are saying about mechanical stress. I do not see anything being linked directly to the occipital muscles besides that being the source of force.


 Their theory is that mechanical stimulation upregulates Hic-5, which in turn activates AR -> TGF-Beta. I'm not missing something am I? 




> Interestingly, a triggering stimulus that can alter the inactive standby status of Hic-5 is the deformation of the cytoskeleton by physical forces;[15,16] therefore, mechanical stimulation can promote overexpression of molecular signals implicated in AGA pathogenesis.


 Tell me what *you* understand by their statement on involuntary muscle contraction. I've given you my opinion on this topic, I'd like to see yours with a bit more justification. The goal is for me to *understand* your point.




> Yes. I mistakenly said "reverses" thought I did not mean it literally. It blunts collagen formation and probably calcification while your cells recycle as per usual. The dermarolling probably speeds this up with wounding and prompting repair of the skin cells, while minoxidil is stopping the fibrosis from happening during repair.


 Do you also agree that TGF-Beta reduction via inhibition of AR can reverse fibrosis?




> I think this is another stretch. Science is very aware of what VEGF is used for and it does not have a strong link to AR. It has a strong link to vascular modeling. This is not just a side function, this is the MAIN function. We can't make these pieces of the puzzle fit to our own agenda.


 When talking about AR and botox relationship I got it from this paragraph in the botox study: They tied Botox to AR, I simply brought their point up to illustrate how AR is so frequently implicated in AR. I proposed a different mechanism for Botox's hair growth promoting effects. 




> Mechanistically, the scalp behaves like a drum skin with tensioning muscles around the periphery. These muscle groupsthe frontalis, occipitalis, and periauricular muscles and to a minor degree the temporaliscan create a tight scalp when chronically active. Because the blood supply to the scalp enters through the periphery, a reduction in blood flow would be most apparent at the distal ends of the vessels, specifically, the vertex and frontal peaks. Areas of the scalp with sparse hair growth have been shown to be relatively hypoxic, have slow capillary refill, and to have high levels of dihydrotestosterone.4Conceptually, Botox loosens the scalp, reducing pressure on the perforating vasculature, thereby increasing blood flow and oxygen concentration. The enzymatic conversion of testosterone to dihydrotestosterone is oxygen dependent. In low-oxygen environments, the conversion of testosterone to dihydrotestosterone is favored; whereas in high-oxygen environments, more testosterone is converted to estradiol.4 Blood flow may therefore be a primary determinant in follicular health. Strategically placed Botox injections appear able to indirectly modify this variable, resulting in reduced hair loss and new hair growth in some men with androgenetic alopecia.
> It's not a coincidence, it definitely is a link in the chain. MOST studies MUST agree AGA is caused by AR from the outset and this is the focus, they do not focus on other pathways. So its not really a coincidence if you are targeting a specific pathway.


 The comment about botox increasing VEGF/HIF-1 was my own suggestion of the mechanism of botox inducing growth, rather than due to botox's muscle paralyzing effect as you initially implied here; Perhaps I misunderstood.




> When I speak about cause I do not mean a single link in a chain, I am speaking about ROOT cause. In this case AR is not the root cause, mechanical stress would be if such a hypothesis were correct. If this could be definitively proven (I'm not saying it is) then would you treat AR as the cause or the tension problem?? It's interesting that the Botox study gets ignored even though the author has been open about it as well.
> http://journals.lww.com/plasreconsur...ulinum.79.aspx


 


> No one has discovered the root cause, thats why we have these hypothesis. PGD2 and immunity are probably downstream of androgen activity in the chain. It maybe multi-factor epigenetic. The monozygotic twin studies show that it IS a factor.


 I was trying to suggest that the genes are the root cause predisposing individuals to AGA, and I believe there isnt a cause originating postnatally as a result of the environment. My rationale is that regardless of the cause, if you prevent the mediator that has detrimental effects on hair, the cause becomes irrelevant. If tension -> AR, then by targeting AR you can kill many birds with one stone. If the root cause (besides gene) is a trigger that sets off the chain, we cant undo it. But we can target active pathways that actively inhibit hair so long as they exert their effects. My methodology is firmly rooted to suppressing AR co-activators and upregulating WNT/Beta Catenin pathways, whereas you believe fibrosis/calcification needs to be addressed.

----------


## UNBEAT

any news from fgf11..

----------


## pixels

> any news from fgf11..


 News? 

What about photographic evidence showing cosmetic improvements?

Oh wait... This guys writes 3 pages of "nigram" blah but not willing to show one image.

----------


## fred970

> News? 
> 
> What about photographic evidence showing cosmetic improvements?
> 
> Oh wait... This guys writes 3 pages of "nigram" blah but not willing to show one image.

----------


## UNBEAT

FGF11 any result man? photos to show??? we are waiting man..

----------


## jamesst11

> 


 Sheldon! hahaha... we should get him on here.  I am certain he can solve this.  :Wink:

----------


## FGF11

I've been trying so many different things. It's a one man thing. I'm sorry, I assure you I want to do thin more than probably anyone in the world. If you want a picture though after editing it, I will update the one that I have soon. It's just basically, few black dots showing in a small area that didn't exist before. I don't think any of you will find that impressive, but those of you who are more life tech savvy will know what I'm talking about. 

To let you know what I've been up to, remember the problems:

1st) It was very expensive and time consuming to make the siRNA's.

2nd) It needed daily injection so after like a week, you would develop wounds.

3rd) you needed quite a lot of material, and could develop side effects. 

Right?

So I've been able to solve all of them, and soon I will try a complete trial on myself.

I'm using a way to permanently deliver genes to my head to kill Androgen Receptor, not just daily injection but once in 2 or 3 month injections. what follows is hard for lay people to understand, so that's why I don't bother updating here, because no one actually knows what I'm writing. Anyways, here is quick update:

I'm using AAV type 2 virus. It's a virus that can efficiency (100%) transfect hair follicles with the gene of interest. I've developed a vector, that has a human shRNA with in it, and it's under a specific promoter, that only get's activated in the skin. 

This virus is absolutely safe. It's called Aden-associated virus. A one time injection of this genetically engineered virus will be able to knockout Androgen Receptor for more than a year, so you don't basically need to take any pills or experience side effects for a year. It also will be very cheap may be about 2000-3000 dollar each year. 

Something like this, is already being sold, but for research. It's hard to explain what I'm about to do in lay terms, and I won't explain everything here as I'm starting my own biotech start-up actually. 


something like this: http://www.vectorbiolabs.com/RVS/shA...n-AR-shRNA-AAV

Three things: I believe in what I do, but you guys should know that a small article you see is published takes four years. I'm just a one person doing my best. But I'm progressing very fast.

----------


## FGF11

What I'm about to do, at the least will be EXTREMELY more effective than fiansteride, RU, and even the post potent anti androgens out there. You don't need to take it daily (but once a year) and it has almost zero side effects. 

I'm also building my own start-up, Some very respectable people have actually offered me some money. But I have so much going on in my life. It takes time. But stay tuned. Maybe you hear a news soon in one of the newspapers  :Stick Out Tongue:

----------


## paleocapa89

Holy shit, that is impressive, I hope you will be fine and I wish you success, can't wait to hear from you again.

----------


## Seuxin

It's very good guy but....what about the FDA process ???

----------


## rbrown

> What I'm about to do, at the least will be EXTREMELY more effective than fiansteride, RU, and even the post potent anti androgens out there. You don't need to take it daily (but once a year) and it has almost zero side effects. 
> 
> I'm also building my own start-up, Some very respectable people have actually offered me some money. But I have so much going on in my life. It takes time. But stay tuned. Maybe you hear a news soon in one of the newspapers


 Good luck with your start-up. What is your gut feeling?Do you think it will reverse a NW7 to a head full of hair or it will only prevent hair loss in the early stages?

----------


## youngin

This sounds dangerous as hell. How can you be sure this will be localized to follicles in the scalp? Even totally knocking out AR in sebaceous glands might **** your hair up. Do you even know if hair will grow without androgen receptors?

----------


## FGF11

> Good luck with your start-up. What is your gut feeling?Do you think it will reverse a NW7 to a head full of hair or it will only prevent hair loss in the early stages?


 To be honest, my hands are very tight. I would say keeps the hair and thickens majority. But AR is not the only thing that I am playing with, and so I'm going to actually go for complete reversal. But I won't be talking about that. Because I will only confuse you guys, but don't expect anything soon.  I'm not going to mention everything here, for many reasons, but AR is not the only gene that I'm playing with. 

There are still many many problems ahead.

----------


## FGF11

> This sounds dangerous as hell. How can you be sure this will be localized to follicles in the scalp? Even totally knocking out AR in sebaceous glands might **** your hair up. Do you even know if hair will grow without androgen receptors?


 That's where the technology I'm using comes in. My gene delivery consists of infection of genes to the scalp, and activating it later with another mechanism (chemical). That's as much information as I can give now. Also, the whole system is under a specific promoter that is only active in skin.

----------


## FGF11

> This sounds dangerous as hell. How can you be sure this will be localized to follicles in the scalp? Even totally knocking out AR in sebaceous glands might **** your hair up. Do you even know if hair will grow without androgen receptors?


 Yes, they will. AR knockout mice not only have thick hair but regenerate skin much faster.

Also, the reason upon balding skin gets more oily and itchy, is that AR cause lineage differentiation of stem cells from hair follicle towards SG. Anyways, I've got to go.

----------


## lol76

Best of luck, FGF11 - and thankyou!

----------


## Westonci

> What I'm about to do, at the least will be EXTREMELY more effective than fiansteride, RU, and even the post potent anti androgens out there. You don't need to take it daily (but once a year) and it has almost zero side effects. 
> 
> I'm also building my own start-up, Some very respectable people have actually offered me some money. But I have so much going on in my life. It takes time. But stay tuned. Maybe you hear a news soon in one of the newspapers


 God bless you  FGF11, your honest to god our only hope in this greedy and corrupt industry.

----------


## Swooping

> Yes, they will. AR knockout mice not only have thick hair but regenerate skin much faster.
> 
> Also, the reason upon balding skin gets more oily and itchy, is that AR cause lineage differentiation of stem cells from hair follicle towards SG. Anyways, I've got to go.


 Doesn´t AAV integrate rather in a site specific fashion. In other words it´s unlikely to spread in the body on it's own right? 

I have read papers about prostate cancer wherein AAV-mediated shRNA was used for AR knockdown

AR knockdown would be godly, like really godly.

Long term lasting 100% preventative treatment. AGA would be eradicated. One can only dream and fantasize about that dude..

But... Can you show some pictures dude? Your set-up or anything convincing, more people will take you seriously. 

Putting it into practice is on a whole different level.

----------


## sdsurfin

Hey FGF11 why don't you hire some interns man? Sounds like you're pretty swamped. Hopefully you can get a whole operation off the ground, there are a lot of people on these forums that could probably lend a hand in some way, at least on the non-scientific aspect of things.  I do think that the only real solution to baldness will come through genetic manipulation. I'm pretty surprised that others are not trying to tackle it from this angle.  I wish you all the luck.  I'm in contact with Dr. Hsu from the follicept team,he's a very capable scientists, and although I don't think that their approach to hairloss is going to work at all, he might be open to collaborating or helping you find resources if he's swayed by your science.  I can't recommend him enough as a person.

----------


## joachim

> Hey FGF11 why don't you hire some interns man? Sounds like you're pretty swamped. Hopefully you can get a whole operation off the ground, there are a lot of people on these forums that could probably lend a hand in some way, at least on the non-scientific aspect of things.  I do think that the only real solution to baldness will come through genetic manipulation. I'm pretty surprised that others are not trying to tackle it from this angle.  I wish you all the luck.  I'm in contact with Dr. Hsu from the follicept team,he's a very capable scientists, and although I don't think that their approach to hairloss is going to work at all, he might be open to collaborating or helping you find resources if he's swayed by your science.  I can't recommend him enough as a person.


 excellent idea. they can profit from each other. knowledge sharing is key in many aspects.

i hope, after what FGF11 has written so far, everyone now sees that he is not the usual bro-science guy who just reads some papers and tinkers around.
this guy has incredible knowledge and works with gene editing and other crazy stuff. maybe his idea will not pan out, but the stuff he is trying is more advanced then we could imagine.
i think he has a realistic chance to develop something useful. if not a full cure, at least something better than fin, minox or RU, without the hassle and side effects.

if more users and professionel chemists/scientists would be like FGF11, hairloss would be a thing of the past by now. there are simply too few scientists working actively on hairloss, and most of them are quacks and charlatans which dance around for years with doing decade-long research with no real results.

----------


## joachim

> What I'm about to do, at the least will be EXTREMELY more effective than fiansteride, RU, and even the post potent anti androgens out there. You don't need to take it daily (but once a year) and it has almost zero side effects. 
> 
> I'm also building my own start-up, Some very respectable people have actually offered me some money. But I have so much going on in my life. It takes time. But stay tuned. Maybe you hear a news soon in one of the newspapers


 man, that's exciting and impressive. i'm glad you have gotten some money to take those things further.

if you can produce some positive results with your technique, probably someone will want to buy your IP or the whole company including you. i hope you don't sell your soul when offered million-dollar-deals from other companies. if you personally have the feeling that you can solve hairloss or at least improve hairloss treatments, please be eager and passionate enough to bring that thing to an end. if your approach is promising you will become a millionaire anyway, one way or another. don't sell your IP for a quick buck. you could make history by beating this decade-lasting nightmare from which millions of people suffer every day. 
it's often the case that small startups are bought and their product gets shelved in favor of selling other worthless crap. it happend in the past with many products/IP in many different areas of life.

i wish you good luck with what you're doing. sounds complicated as hell, but i have a good feeling you're a pro at those tasks. keep us in the loop please.

----------


## FGF11

-

----------


## fred970

Thank you for curing hair loss, random internet guy with no medical degree!

----------


## UNBEAT

I WANT TO THANK YOU FGF11 FOR WHAT ARE YOU DOING ANDFOR YOUR TIME TO REPLY TO US.i want to say that if it is possible to let us know if there is any new important update in what you are doing And sell to us guys of BT the cure even it is not fda aproven ...
We are with you

----------


## Seuxin

Hello,

Don't want to play the Devil's advocate but if you succed to solve baldness, it will cost :

2-3000 / year ( it's a lot !)
You will need to deal with FDA, so...5-10 years ?

----------


## BaldingEagle

> Thank you for curing hair loss, random internet guy with no medical degree!


 Medical degree isn't even nearly enough. I have a masters in molecular biology, bachelors in physical chemistry and my brother has a PhD and neither of us whom are both suffering hair loss have any real idea how the exact process works after extensively looking at all known research and pathways.

Trying to cure your natural genetic process without editing the gene itself is far more difficult than these armchair scientists can even comprehend.

It's a miracle we even have things like fin min and dut.

----------


## FGF11

> Doesn´t AAV integrate rather in a site specific fashion. In other words it´s unlikely to spread in the body on it's own right?


 Actually these ones don't integrate. That's why I said 2 month to one year, one injection would have been enough for the life time if integrated. However, integration is unpredictable as a potent promoter may go behind an oncogene and cause cancers. It's an episomal technology, that stays in nucleus for months to years. Depending on the way it was built.




> Thank you for curing hair loss, random internet guy with no medical degree!


  bear with me, haha someday you will know my true identity and you many feel a bit wired for saying these. I never said I have the cure. It'll be an effective treatment, however.




> I WANT TO THANK YOU FGF11 FOR WHAT ARE YOU DOING ANDFOR YOUR TIME TO REPLY TO US.i want to say that if it is possible to let us know if there is any new important update in what you are doing And sell to us guys of BT the cure even it is not fda aproven ...
> We are with you


  Selling, do you think I would ever do that?! never


Dr. Who?! I don't actually need collaborations as of now, I have enough on my plate. 

Tnx everyone, But please don't get your hopes up yet.

----------


## BaldingEagle

> Actually these ones don't integrate. That's why I said 2 month to one year, one injection would have been enough for the life time. However, integration is unpredictable as a potent promoter may go behind an oncogene and cause cancers. It's an episomal technology, that stays in nucleus for months to years. Depending on the way it was built.
> 
>  bear with me, haha someday you will know my true identity and you many feel a bit wired for saying these. I never said I have the cure. It'll be an effective treatment, however.
> 
>  Selling, do you think I would ever do that?! never
> 
> 
> Dr. Who?! I don't actually need collaborations as of now, I have enough on my plate. 
> 
> Tnx everyone, But please don't get your hopes up yet.


 By all means continue with your project and prove us wrong. Until then anyone with a brain would be somewhat skeptical.

----------


## FGF11

> By all means continue with your project and prove us wrong. Until then anyone with a brain would be somewhat skeptical.


 I, myself, am skeptical as well. 

actually everyone must be very skeptical.

 I have not started anything yet (the actual self trial), so there is no reason to lie. 

On paper though, and based on what I know from a small experiment, I have my hopes high and actually my fingers crossed.

----------


## Sogeking

double.

----------


## Sogeking

Hey Fgf I'll tell you what I tell everyone who comes along with a potential new treatment: try it out but give us proof. Pictures, results, numbers comparions with existing treatments and placebo. I hope it works, I wish you the best of luck but the burden of proof is on you.

This is the same I said about Follicept. I am glad they tried but they haven't proven it works. However that just means we need more people trying.

----------


## Hairmore

Fgf, perhaps you can convince some chemist or group of scientist of your idea and you could test it somehow together. I would love to know if it really works. I am also not convinced without any images.

----------


## InBeforeTheCure

> But AR is not the only thing that I am playing with, and so I'm going to actually go for complete reversal. But I won't be talking about that. Because I will only confuse you guys, but don't expect anything soon.


 Pls tell. We can deal with confusion.  :Big Grin: 

Unless of course you're concerned about others stealing your ideas. Then it's best not to say, of course.

----------


## Hemo

Good luck friend

----------


## Westonci

> Hey FGF11 why don't you hire some interns man? Sounds like you're pretty swamped. Hopefully you can get a whole operation off the ground, there are a lot of people on these forums that could probably lend a hand in some way, at least on the non-scientific aspect of things.  I do think that the only real solution to baldness will come through genetic manipulation. I'm pretty surprised that others are not trying to tackle it from this angle.  I wish you all the luck.  I'm in contact with Dr. Hsu from the follicept team,he's a very capable scientists, and although I don't think that their approach to hairloss is going to work at all, he might be open to collaborating or helping you find resources if he's swayed by your science.  I can't recommend him enough as a person.


 
Hey FGF11, I live in Toronto. If you live here, I can volunteer my time to help your cause. Will do anything to help you.

----------


## jjo

> Hey Fgf I'll tell you what I tell everyone who comes along with a potential new treatment: try it out but give us proof. Pictures, results, numbers comparions with existing treatments and placebo. I hope it works, I wish you the best of luck but the burden of proof is on you.
> 
> This is the same I said about Follicept. I am glad they tried but they haven't proven it works. However that just means we need more people trying.


 leave him alone and stop asking for pics and proof...the guys working on it and obviously wants this. he hasn't made any promises  i'm sure when he has something to report he will, pics will come later.

thanks FGF11 for all your time and effort.

----------


## burtandernie

The low hanging fruit for cures and treatments is long gone. No one is going to scribble down the cure for MPB on the back of a napkin somewhere its way too hard for that. No one guy is going to hack together the cure for MPB.
A lot of things that in theory could or should work dont in practice ever amount to much if anything. Putting theory into a practical compound that works is really where the rubber meets the road. Easier said than done. Only 2 companies have ever done it.

----------


## FGF11

-

----------


## joachim

> The low hanging fruit for cures and treatments is long gone. No one is going to scribble down the cure for MPB on the back of a napkin somewhere its way too hard for that. No one guy is going to hack together the cure for MPB.
> A lot of things that in theory could or should work dont in practice ever amount to much if anything. Putting theory into a practical compound that works is really where the rubber meets the road. Easier said than done. Only 2 companies have ever done it.


 the difference is: this guy tests his theories directly and immediately on himself, because he knows what is dangerous and what not. he knows the risk and he has the know-how to test different things in a safe way on himself. 
he doesn't have to do years of tests on mice and go through clinical trials and first find investors who give him millions of dollar to test a theory.
if he knows the science and has access to tools and materials, which all seems to be the case, then he could get very far if he is eager and passionate enough. with the right effort, a single person can get much further than all those so-called hair researchers who spend years and millions of money without real progress. most of them have a full head of hair, so they are not in a hurry to find an effective cure. just tinkering in their labs, year after year, publishing meaningless papers and tests on mice which never work on humans.

----------


## FGF11

> the difference is: this guy tests his theories directly and immediately on himself, because he knows what is dangerous and what not. he knows the risk and he has the know-how to test different things in a safe way on himself. 
> he doesn't have to do years of tests on mice and go through clinical trials and first find investors who give him millions of dollar to test a theory.
> if he knows the science and has access to tools and materials, which all seems to be the case, then he could get very far if he is eager and passionate enough. with the right effort, a single person can get much further than all those so-called hair researchers who spend years and millions of money without real progress. most of them have a full head of hair, so they are not in a hurry to find an effective cure. just tinkering in their labs, year after year, publishing *meaningless papers* and tests on mice which never work on humans.

----------


## joachim

hey FGF11, i was wondering: do you have the tools and are you able to analyze dermal papilla cells in terms of gene expression? if you are aiming at full regrowth, does this involve some culturing (multiplication) of cells? 
i'm not sure if you are aware of all the culturing attempts in the past as you are probably not long enough on the forum.
researchers like jahoda, christiano, and other labs tried to multiply DP cells but none of them succeeded as it turned out the cells lose inductive capabilities and gene expression levels of some genes. 
some recent papers seem to indicate that there was progress regarding this but there's no clear answer to that yet. maybe you've seen the other recent thread about the nanocoating which seem to allow the cells to expand and retaining all the necessary properties. however, there is no exact comparison of before/after gene expression levels so this may still be not a full success. i don't know.

are you aware of those issues? does your approach even need some culturing of cells?

----------


## FGF11

Yes, I'm aware about them. 

The first cell therapies for skin was actually developed by Howard Green. He, unfortunately, died. But what he did was, he cultured epithelial human cells in a very specific way. In which, he added the media from under, and layers of epithelia grew out and then he developed autologous cell transplantation. This gave rise to few companies, one of them was named Organogenesis, which developed substitute skins but the company went bankrupt because first. Many of the famous skin biologists today are trained in his lab, including elaine fuchs, which she has trained many others including Dr. Rendl, Dr. Greco, ..

In response to a question, he says the following:

"It's worth noting that at the time we did the initial skin graft experiments, the US Food and Drug Administration (FDA) existed, but they were not interested, and there were no committees whose approval you had to seek. We went ahead with this without any impediments of that sort. Within a few years, I could not do an experiment on a mouse without committee approval, so that's how the situation changed within a short period of time. If I had needed to face that at the beginning, I wouldn't have started the whole thing because it's just too much to deal with."

So even prominent scientist are actually happened by FDA in many ways. 

Colin Jahoda, was among the first scientist, who showed that dermal papillae can induce hair follicle regeneration. At the time, he was working at Dr. Reynolds lab, which was a pioneer in hair follicle studies. He has also trained many of Many other scientists, such as Dr. Christiano, which she has Trained Dr. Higgins, and so on. Dr. Jahoda, first transplanted a hair follicle to his wife's hand and showed that dermal papillae can induce hair follicles. 

However, later on works from Dr. Mc Elwee showed that derma sheath cells are more important than dermal papillae cells. Dermal papillae cells never actually divide in vivo, so they must come from somewhere. After recent studies, By Dr. Bernieskie, (was trained in Dr. Freda miller lab) he showed that actually Dermal sheath cells contribute to dermal papillae, and dermal papillae is not the important one.


So replicel seems to be on the right track here. Since aderans and intercytex were trying to use dermal papillae (as what Dr. Christiano and Higgins) are trying to do. However replicel is culturing dermal sheath cells.

However, guaranteed it won't work.

Why? you may ask?

Hematopoietic stem cells have been known for 50 years or so, and tons of more research is being done on them for bone marrow transplantation studies. We do have Hematopoietic stem cell for quite a decade now, however, despite 10X more knowledge on them than hair follicle stem cells. Scientists have not yet been able to culture these stem cells. It's not possible. Replicell is on the right track, but it'll take 50 more years for them to learn how to culture these cells. They will differentiate so fast and irreversibly since they are out of their niche. 

If some one finds a way to culture Hematopoietic stem cells, he could save millions of people every year. But alas it's not yet feasible. So is hair follicle stem cell culture.


As for cell coating, those are jokes. They are not useful in any sense. The only real use I see, is to some how use them to coast stem cells from other people, or may be embryonic stem cells  used by histogen (so these cells would become immune protective) and transplant them back to the hair. So they will secrete growth factors in the head, while the body won't attack them.


This is not something fancy, as viacyte is doing the exact same thing, they're using some one else's embryonic stem cells but they put it in a protective sheet and implant it in the body. They're using it to cure diabetes. They are in clinical trials. As for diabetes, no one has still find a way to replicate those stem cells as well. and we know tons more about beta-cells than any other cells.

So my take, it won't happens soon. Dr. Paul kemp was the smartest and given up on that long ago.

A simple gene analysis will take years if I want to do, and so no I can't do that. Also, I know, even if I try I would fail to keep inductivity of dermal papillae or dermal sheath cells, It's gigantic task. 
It's nothing short of miracle.

----------


## FGF11

There are a lot of big problems in this world, that hair loss, sometimes seems actually quite small compared to them. Watch The Boy Whose Skin Fell Off, and  My Flesh and Blood  just to get an idea of how a disease such as Epidermolysis bullosa can be soooooooooo much worse than hair loss. So please stay positive.  :Smile:  and be grateful for what you are and have in life but also don't sit on your butt  :Stick Out Tongue:  

I'm taking a real break from this for maybe a month or two. I need some refreshing.

----------


## FGF11

For the regrowth, I can't talk about it now. But rest assured it's something new, that no one has tried ever before. But it's crazy, so I need to do it first in mice, and so I have no resources to do that. Unless, I start legitly working on this in a legit lab, and it might take years.

life's short, it sucks.  :Frown:

----------


## joachim

> For the regrowth, I can't talk about it now. But rest assured it's something new, that no one has tried ever before. But it's crazy, so I need to do it first in mice, and so I have no resources to do that. Unless, I start legitly working on this in a legit lab, and it might take years.
> 
> life's short, it sucks.


 but wouldn't this be a good opportunity to work together with other researchers where you would have access to a lab and mice and everything which is required. Dr. Hsu from Follicept was mentioned in a recent post. i could imagine he could be very interested if you talk to him about your idea. together you could achieve results much faster, and he is also a brilliant and nice guy. he's also doing various tests on mice so i think he should have a lab and a license to do all that with mice.
but that's just idea... it's up to you of course. as you mentioned the open science aspect i assume you are interested in collaborations with other researchers.

BTW where are you located? somewhere in europe? just curious

----------


## Follisket

> There are a lot of big problems in this world, that hair loss, sometimes seems actually quite small compared to them. Watch The Boy Whose Skin Fell Off, and  My Flesh and Blood  just to get an idea of how a disease such as Epidermolysis bullosa can be soooooooooo much worse than hair loss. So please stay positive.  and be grateful for what you are and have in life but also don't sit on your butt


 Oh, ffs, not this again.

----------


## kim889

> So replicel seems to be on the right track here. Since aderans and intercytex were trying to use dermal papillae (as what Dr. Christiano and Higgins) are trying to do. However replicel is culturing dermal sheath cells.
> 
> However, guaranteed it won't work.


 What do you mean when you say Replicel won't work? This process has never been done before. 
I don't believe they will release a product which doesn't work...

----------


## Swooping

> 


 Elon musk that genius has a answer to everything. Look he can even regrow his hair magically;

----------


## Hicks

I seen a clip of musk speaking and he just about had an under cut and no sign of any work. Wish I could find it

----------


## sdsurfin

> Yes, I'm aware about them. 
> 
> The first cell therapies for skin was actually developed by Howard Green. He, unfortunately, died. But what he did was, he cultured epithelial human cells in a very specific way. In which, he added the media from under, and layers of epithelia grew out and then he developed autologous cell transplantation. This gave rise to few companies, one of them was named Organogenesis, which developed substitute skins but the company went bankrupt because first. Many of the famous skin biologists today are trained in his lab, including elaine fuchs, which she has trained many others including Dr. Rendl, Dr. Greco, ..
> 
> In response to a question, he says the following:
> 
> "It's worth noting that at the time we did the initial skin graft experiments, the US Food and Drug Administration (FDA) existed, but they were not interested, and there were no committees whose approval you had to seek. We went ahead with this without any impediments of that sort. Within a few years, I could not do an experiment on a mouse without committee approval, so that's how the situation changed within a short period of time. If I had needed to face that at the beginning, I wouldn't have started the whole thing because it's just too much to deal with."
> 
> So even prominent scientist are actually happened by FDA in many ways. 
> ...


 I feel like we need a fact checker here. All you've done so far is come on here, say you have a miracle treatment that you can't say anything about, provide any evidence for, and then shit on everyone else's work.  Maybe you're legit and onto something, but you may just be some obsessive schizo who thinks he knows everything and is just making shit up.

How are coatings for DP cells "useless"?? they just showed in a published paper (where are your publications?) that the coatings restore a huge amount of inductivity to DP cells.  Useless? Christiano just showed that she can restore a massive amount of inductivity (she showed proof in photos) to DP cell spheres just using JAK inhibitors, so the idea that they could restore good enough inductivity for hair growth doesn't seem that unrealistic.  Tsuji seems to be making pretty solid progress on that front too, and has never mentioned hematopoietic stem cells. 

Also what do hematopoietic stem cells have to do with hair? I can't find a single paper that talks about this, and even if they are one of the key stem cell types in the hair follicle, replicel has stated many times that the DSC cells are crucial in maintaining and feeding stem cell populations in the follicle.  

Why should we listen to absolutely anything you say, seeing as we have zero idea who you are, what you're up to, or what qualifies you to know more than people like the researchers at replicel.  Everything that you've said you could have dug off the internet, except for your big claims that other things won't work, and which you have not elaborated on at all. I wish you luck with whatever your experiments are, but if you're gonna come on here and naysay the work of other scientists who are good enough to be open and public about their work and research, then at least elucidate a bit.

----------


## sdsurfin

ah i see now you were just likening the culture of Hematopoietic stem cells to hair cells as far as the challenges concerned.  I don't think this is a good analogy.  Hematopoietic stem cells (HSC) cannot be easily observed directly, and, therefore, their behaviors need to be inferred indirectly. Hair follicle cells can be easily observed and multiplied, and DSC cells do not lose their characteristics.  The stem cells in the scalp are always there, and DSC and DP cells work to maintain them. so the challenges are very different than cloning and repopulating hematopoietic cells.  It would be much more accurate to compare hair follicle cell treatments to a bone marrow transplantation, which scientists can carry out currently and does work. I don't think anyone is going to restore hair to a bald scalp using replicel's techniques, but where there are already functioning stem cell populations, and weakening hair, DSC cells could in fact restore those stem cells to good use. In this scenario, your comparison to the culture of hematopoietic stem cells in vitro really has no correlation. Also, scientists are in fact working on culturing hematopoietic stem cells in vitro, so even that is not a distant dream.  

This is what I'm saying about your arguments. You may be a knowledgeable scientist, but you come on here and make false inferences, and people will believe you because you can throw out fancy terms and unproven ideas.  In the end all you are stating are unproven and at best loosely-thought out opinions on other peoples' research.

----------


## FGF11

I'm not trying to use fancy words. Bone marrow transplantation is more like hair transplantation.

Don't even start me on, Tsuji paper.



What he did is actually not that novel (in the sense of hair follicle engineering and de novo genesis), like not at all. I'm sorry but it's true.

He used Intact human DP to form hair. Guess what Oliver showed decades ago, it's possible to do that. Believe it or not, publishing fancy articles, has a lot to do with how you write the article and mostly not your data.

In another experiment, he used fetal dermal cells, which is known to induce hair follicle. Without the need to co-culture them with Epithelial Bulge stem cells. 

*I never ever said I have the cure. NEVER.* I'm here to introduce real expectations rather than raising false hope.

----------


## FGF11

I'm not trying to use fancy words. Bone marrow transplantation is more like hair transplantation.

Don't even start me on, Tsuji paper.



What he did is actually not that novel (in the sense of hair follicle engineering and de novo genesis), like not at all. I'm sorry but it's true.

He used Intact human DP to form hair. Guess what Oliver showed decades ago, it's possible to do that. Believe it or not, publishing fancy articles, has a lot to do with how you write the article and mostly not your data.

In another experiment, he used fetal dermal cells, which is known to induce hair follicle. Without the need to co-culture them with Epithelial Bulge stem cells. 

*I never ever said I have the cure. NEVER.* I'm here to introduce real expectations rather than raising false hope.

----------


## sdsurfin

> I'm not trying to use fancy words. Bone marrow transplantation is more like hair transplantation.
> 
> Don't even start me on, Tsuji paper.
> 
> 
> 
> What he did is actually not that novel (in the sense of hair follicle engineering and de novo genesis), like not at all. I'm sorry but it's true.
> 
> He used Intact human DP to form hair. Guess what Oliver showed decades ago, it's possible to do that. Believe it or not, publishing fancy articles, has a lot to do with how you write the article and mostly not your data.
> ...


 ?? 
Did I even ask about Tsuji? This is what I'm saying, you come on here and throw out some speculative unexplained theory you have going, but do not engage in any kind of discourse when you make overreaching claims about other peoples' work. You ignored everything I wrote, and have no basis for your claims that nothing else will work.  Just because what Tsuji is doing is not new doesn't mean it will not work. If anything it's encouraging that he is working to perfect things that we know can possibly be a solution.   I think that they are actually very close to maintaining inductivity in hair cells, and from there its really more of an engineering problem than a case of having to publish more papers.

----------


## NeedHairASAP

> ?? 
> Did I even ask about Tsuji? This is what I'm saying, you come on here and throw out some speculative unexplained theory you have going, but do not engage in any kind of discourse when you make overreaching claims about other peoples' work. You ignored everything I wrote, and have no basis for your claims that nothing else will work.  Just because what Tsuji is doing is not new doesn't mean it will not work. If anything it's encouraging that he is working to perfect things that we know can possibly be a solution.   I think that they are actually very close to maintaining inductivity in hair cells, and from there its really more of an engineering problem than a case of having to publish more papers.


 SDsurfin, I feel like he has given a decent explanation of his theory and what he is doing.

And he's just pointing out that Tsuji may not be the gods that most non-scientific bald people think.

People who have never published an academic paper think it's the biggest deal in the world... and it is a long-hard process....but it's not really as impressive as most people think once you've done it.

Not saying to ignore papers, just that they should be taken with a larger grain of salt than most would think.

FG11's theory doesn't seem that far out or confusing to me. I couldn't replicate it or explain it in detail myself, but to me, it at least passes the smell test and is worth hearing more about (and doing so politely)

----------


## allTheGoodNamesAreTaken

For ****'s sake. If it can be tried then try it, document it, come back in a few months or more and post about what happened. All this back and forth speculation is worthless.

----------


## jamesst11

https://www.youtube.com/watch?v=m84cOOc8-T0  FGF11 have you seen this video?

----------


## sdsurfin

I'm not naysaying his theory (even though he retracted his entire first approach and now has something else mysterious in the works.) I'm just pointing out that he has pooh-pooed every other team working on hairloss and said that nothing else will work- based on zero factual evidence- and backs it up with nonsense like "constructing hair follicles is not going to happen because Hematopoietic stem cells are better known and have not been used to cure blood diseases". These things do not correlate, they involve totally different cells and sets of challenges. You can't even see hematopoietic stem cells.  If you're gonna come on here and slam replicel or Tsuji, then at least give good reasons. If you're gonna come on here and say you have a great idea, then explain it and show some evidence. Otherwise you just crush peoples' hopes without any evidence of what you're saying.. 

 Zero of what he has claimed about other treatments makes any sense whatsoever, and he sure hasn't explained why his is going to work or shown any proof. Everybody knows scientific papers don't mean shit. Everyone knows that the things Tsuji and jahoda and Christiano are working on have been in the works forever. that doesn't mean they arent a lot closer to being able to do real things.

On the flip side, Dr. Robert Hoffman was trying to fix hairloss with gene introduction in like 1995 with no results. I wish FGF11 the best with whatever he's doing, but if his science is only as solid as his writing or his logical analysis of other teams' work, then I doubt he'll get too far.

----------


## UNBEAT

i think fgf11 has understood the essence of the hair loss problem and he will get far,because this brakethough like hair loss are done by courageous individual reserchers

----------


## NeedHairASAP

> I'm not naysaying his theory (even though he retracted his entire first approach and now has something else mysterious in the works.) I'm just pointing out that he has pooh-pooed every other team working on hairloss and said that nothing else will work- based on zero factual evidence- and backs it up with nonsense like "constructing hair follicles is not going to happen because Hematopoietic stem cells are better known and have not been used to cure blood diseases". These things do not correlate, they involve totally different cells and sets of challenges. You can't even see hematopoietic stem cells.  If you're gonna come on here and slam replicel or Tsuji, then at least give good reasons. If you're gonna come on here and say you have a great idea, then explain it and show some evidence. Otherwise you just crush peoples' hopes without any evidence of what you're saying.. 
> 
>  Zero of what he has claimed about other treatments makes any sense whatsoever, and he sure hasn't explained why his is going to work or shown any proof. Everybody knows scientific papers don't mean shit. Everyone knows that the things Tsuji and jahoda and Christiano are working on have been in the works forever. that doesn't mean they arent a lot closer to being able to do real things.
> 
> On the flip side, Dr. Robert Hoffman was trying to fix hairloss with gene introduction in like 1995 with no results. I wish FGF11 the best with whatever he's doing, but if his science is only as solid as his writing or his logical analysis of other teams' work, then I doubt he'll get too far.


 
Well, to be fair. All of these teams have been around a long time and nothing has worked.... what more evidence do you need lol?

Of course that's not to say they won't succeed in the future, but their track record doesn't exactly instill confidence and isn't what I'd call evidence against fg11 poo pooing them...

also half of what he's saying is that they don't move fast enough, not so much that their theories are totally flawed.. just that at their pace and given the angles they are taking, they're unlikely to succeed anytiem soon.

----------


## NeedHairASAP

> I'm not naysaying his theory (even though he retracted his entire first approach and now has something else mysterious in the works.) I'm just pointing out that he has pooh-pooed every other team working on hairloss and said that nothing else will work- based on zero factual evidence- and backs it up with nonsense like "constructing hair follicles is not going to happen because Hematopoietic stem cells are better known and have not been used to cure blood diseases". These things do not correlate, they involve totally different cells and sets of challenges. You can't even see hematopoietic stem cells.  If you're gonna come on here and slam replicel or Tsuji, then at least give good reasons. If you're gonna come on here and say you have a great idea, then explain it and show some evidence. Otherwise you just crush peoples' hopes without any evidence of what you're saying.. 
> 
>  Zero of what he has claimed about other treatments makes any sense whatsoever, and he sure hasn't explained why his is going to work or shown any proof. Everybody knows scientific papers don't mean shit. Everyone knows that the things Tsuji and jahoda and Christiano are working on have been in the works forever. that doesn't mean they arent a lot closer to being able to do real things.
> 
> On the flip side, Dr. Robert Hoffman was trying to fix hairloss with gene introduction in like 1995 with no results. I wish FGF11 the best with whatever he's doing, but if his science is only as solid as his writing or his logical analysis of other teams' work, then I doubt he'll get too far.


 He has a theory about a protocol that could shut off the AR.

What more is there to explain?

----------


## fred970

> i think fgf11 has understood the essence of the hair loss problem and he will get far,because this brakethough like hair loss are done by courageous individual reserchers


 Yeah, f-ck the qualified scientists who are on this. The cure for hair loss will be found in FGF11's basement!

----------


## jamesst11

> Yeah, f-ck the qualified scientists who are on this. The cure for hair loss will be found in FGF11's basement!


 It just might Fred, it just might.  Sometimes the most intuitive minds and greatest discoveries come from outside the lab.  How do you know FGF11 isn't like Matt Damon in, "a beautiful mind"?   :Big Grin:

----------


## fred970

> It just might Fred, it just might.  Sometimes the most intuitive minds and greatest discoveries come from outside the lab.  How do you know FGF11 isn't like Matt Damon in, "a beautiful mind"?


 You just mixed up Russel Crow with Matt Damon and A Beautiful Mind with Good Will Hunting.

----------


## x4342

> You just mixed up Russel Crow with Matt Damon and A Beautiful Mind with Good Will Hunting.


 Indeed, and the distinction is everything.   :Wink: 

Is he saying that FGF11 is a brilliant scientist who could cure hair loss if only he had a good psychologist?  -Or is he saying that FGF11 thinks he's cured hair loss and has a full head of hair while the rest of the world sees him as a schizophrenic Norwood 6?

----------


## jamesst11

> You just mixed up Russel Crow with Matt Damon and A Beautiful Mind with Good Will Hunting.


 hahaha... o.k. o.k. fair enough.  I am just too bitter against all the NW1's that I confuse them.

----------


## jamesst11

> You just mixed up Russel Crow with Matt Damon and A Beautiful Mind with Good Will Hunting.


 hahaha... o.k. o.k. fair enough.  I am just too bitter against all the NW1's that I confuse them.

----------


## jjo

> Yeah, f-ck the qualified scientists who are on this. The cure for hair loss will be found in FGF11's basement!


 +1

----------


## pixels

> +1


 Maybe Nigram and FGF11 could have a sleep over and solve all our problems. 

If FGF11 just added acell to his basement solution we might be onto a winner.

Look out for the photographic evidence coming at you via a pixel art blog in India.

----------


## fred970

> Maybe Nigram and FGF11 could have a sleep over and solve all our problems. 
> 
> If FGF11 just added acell to his basement solution we might be onto a winner.
> 
> Look out for the photographic evidence coming at you via a pixel art blog in India.


 It's funny how people never learn. How many pages was the Nigam thread?

----------


## Hairmore

> Indeed, and the distinction is everything.  
> 
> Is he saying that FGF11 is a brilliant scientist who could cure hair loss if only he had a good psychologist?  -Or is he saying that FGF11 thinks he's cured hair loss and has a full head of hair while the rest of the world sees him as a schizophrenic Norwood 6?


 A norwood 6 who still gets the nobel price in the end because his ideas were used by the entire industry and became the new standard for treating hair loss.

----------


## FGF11

look, my tolerance for stupidity is low. So please stop posting none sense here. 

Also guess what?! if you stop posting to this thread, this thread won't grow in pages, and I will stop receiving emails telling me I have nonsense posted on this thread. Okay? 

Meanwhile, you can read one of the examples of self-experimentation that actually led to Nobel Prize in Medicine:

http://blogs.scientificamerican.com/...ri-and-ulcers/

(if you can read two pages of something that is not related to wallowing in self-pity ofcoures) .

and stop comparing me with charlatans who try to sell you stuff.

I noticed in another thread, just above mine,  people are referring others to products in amazon with next to zero scientific evidence and gaining commission through referrals. How lowly is that?!

so unless I try to sell you something, or refer you, or raise false hope, please stop being a downer and a dummy, and stop posting in this thread for fck's sake.

----------


## pixels

Here what you sell is hope. This site has teenage members suicidal and sad.

If what you're selling turns out to be mumbo jumbo you deserve to have your ass kicked  :Wink: 

I hope you're right.

----------


## jjo

hey FGF11, we haven't heard from you in a while.. hows the study going?

----------


## FGF11

A vial of lentiviral vectors I have created is sitting somewhere close and I’m arguing to either intradermally inject them or not. I have not yet made the decision. This vial of lentiviral vectors can potentially (with a high probability) bring my hair back at the site of injection, but as of now, I don’t have the balls to do it. I already had AAV antigens, so couldn’t use them. I’ve developed a lentiviral system using a bi-cistronic expression of shRNA and a catalytically dead CRISPIR (CRISPRi) both targeting AR in a VSV-G-pseudotyped replication-deficient lentivirus. But I don’t know what can happen upon injection, I simply don’t have the balls. This can silence AR probably up to 99% for a couple of years or more but can also cause cancer, with a low probability, but that can happen. There is almost a zero chance for the virus to go systemic. My lentiviral genes are under strong promoters and these promoters can sit in wrong places when integration happen and purely out of murphy's law cause cancer. You guys probably have absolutely no idea what I wrote here but that's the current state of affairs.

----------


## fred970

Thanks Dr. Nigam!

----------


## Link Mahboi

> Thanks Dr. Nigam!


 Oh please, just shut up.

----------


## Link Mahboi

> A vial of lentiviral vectors I have created is sitting somewhere close and I’m arguing to either intradermally inject them or not. I have not yet made the decision. This vial of lentiviral vectors can potentially (with a high probability) bring my hair back at the site of injection, but as of now, I don’t have the balls to do it. I already had AAV antigens, so couldn’t use them. I’ve developed a lentiviral system using a bi-cistronic expression of shRNA and a catalytically dead CRISPIR (CRISPRi) both targeting AR in a VSV-G-pseudotyped replication-deficient lentivirus. But I don’t know what can happen upon injection, I simply don’t have the balls. This can silence AR probably up to 99% for a couple of years or more but can also cause cancer, with a low probability, but that can happen. There is almost a zero chance for the virus to go systemic. My lentiviral genes are under strong promoters and these promoters can sit in wrong places when integration happen and purely out of murphy's law cause cancer. You guys probably have absolutely no idea what I wrote here but that's the current state of affairs.


 FGF11, I understand the risks and can comprehend if you decide to not do it, but just think how this could change the game for us and for good if that works, I believe some things are worth a leap of faith.

----------


## UNBEAT

FGF11 
i have a bit the idea what you are saying because i have read about siRNA and silencing genes.But is there a way to prove if this work and doesnt cause cancer without injecting yourself, like using a mouse or something else.
Is there a way to prevent these promoters causing cancer?
excuse me for maybe ignorance questions but i want to understand a bit more.

P.S. i have no deep knowledge in medicine because is not my field but i have read a bit this times especially for hair loss and thank you for what you're doing

----------


## paleocapa89

Well if he inject himself and succeed the best case scenario would be stopping his hairloss. Even then skeptics could say that maybe he's natural balding process just stopped, and there would be probably no definitive answer to disprove them. 

If the technique indeed stopped his hairloss, that would be huge, but probably there would be no way for average joe's to replicate what he did. To make such a thing commercially available it would probably have to go through at least 10 years of testing right?

And in the worst case scenario he gets cancer? That doesn't sound too good..

----------


## Link Mahboi

well, he said that it could also regrow his hair.

----------


## Chemical

> and stop comparing me with charlatans who try to sell you stuff.
> 
> I noticed in another thread, just above mine,  people are referring others to products in amazon with next to zero scientific evidence and gaining commission through referrals. How lowly is that?!
> 
> so unless I try to sell you something, or refer you, or raise false hope, please stop being a downer and a dummy, and stop posting in this thread for fck's sake.


 This other thread where "people are referring others to products in amazon" I believe is mine. I'm the one whos posting links to products on amazon after people have requested links to exact products.

I'm not in the habit of commenting if I dont have anything good to say but I feel like you've insulted my integrity here which I take very seriously. 

I was curious if my links really did contain referrals or affiliate codes without me realising, so I did some "research" on this matter.




> For example, you must include your Associates ID or “tag” (appearing as XXXXX-20, or such other format as we may designate) as a parameter in the URL of each link you place on your site to the Amazon Site. In addition, you must not use a link shortening service in a manner that makes it unclear that you are linking to an Amazon Site.
> 
> https://affiliate-program.amazon.com...rating/linking


 


> There are two type of short URLs that you can create for your Amazon affiliate links. The first one uses Amazon.com domain name.
> You need to simply add: */dp/yourproductid/?tag=youraffiliatetag.*
> 
> Take a look at this example:
> http://amazon.com/dp/0470560541/*?tag=wpb09-20*
> 
> You can create an even shorter URL by using amzn.com domain name. Simply remove the /dp/ prefix and add your product id with your affiliate tag.
> http://amzn.com/0470560541/*?tag=wpb09-20*
> 
> http://www.wpbeginner.com/wp-tutoria...-in-wordpress/


 


> [–]sludgem 5 points 3 years ago 
> 
> The "tag" numbers are the only affiliate codes you need to worry about.
> The ref codes are a different kind of referral, they help amazon keep track of how you move throughout the site. In this case, "pd_sim_watch_4" means you got to that page from the product description of another item by clicking the fourth thing in the "similar items" section.
> 
> https://www.reddit.com/r/amazon/comm...identify_them/


 To help you out, I've posted a few of my links here so we can make sure if they contain these affiliate tags: (You can verify the original posts too)




> *@SriHanuman*
> 
> If its within your budget you will better off with a custom vehicle using this ethyl alcohol from amazon uk:
> amazon.co.uk/Spinnrad-Ethyl-Alcohol-96-5%25-100/dp/B001TJ0NJY/ref=sr_1_1?ie=UTF8&qid=1451336373&sr=8-1&keywords=ethyl+alcohol
> 
> mixed with this PG:
> amazon.co.uk/1000ml-Classikool-Propylene-Glycol-Pharma/dp/B00BHGM05O/ref=sr_1_1?ie=UTF8&qid=1451336492&sr=8-1&keywords=propylene+glycol
> 
> That premade tincture wont be as effective as a custom Ethanol/PG vehicle.
> ...


 


> If you're in the US:
> 
> Amazon US - Oleuropein - $7.99
> amazon.com/Olive-Leaf-Extract-Super-Strength/dp/B00GZRIW5C/ref=sr_1_1?ie=UTF8&qid=1451417068&sr=8-1&keywords=oleuropein
> 
> Amazon US - Propylene Glycol - Pick whichever is cheapest
> amazon.com/s/ref=nb_sb_noss?url=search-alias%3Daps&field-keywords=propylene+glycol&rh=i%3Aaps%2Ck%3Apropyle  ne+glycol
> 
> For those that want to use minox:
> ...


 I'm trying to find these affiliates tags but I cant... Maybe you can help us out?

I'm very fortunate t not have to worry about money, this isnt my job, I only do this because I want to grow hair. I dont want to make a single penny off this and do not like the idea of any company trying to sell whats supposed to be free. You might not have read my thread fully but I'm sure alot of people will agree with me on this that every single product I've recommended has at least one study documenting its direct or indirect effect on positively modulating hair growth.

I've noticed you've got a pattern of making outlandish claims without supporting your statements with references or clear, well explained line of reasoning. And when people try and constructively criticise your work, instead of trying to come to an understanding - you get defensive. Next time if youre going to make derogatory statements against other people and their work I suggest you take the time to do your research and verify your facts - otherwise you'll just end up embarassing yourself. Especially since you're the one making big claims, this behaviour really isnt helping your credibility seeing as its being questioned. I didnt mean to come across as harsh but I hope you will take this as objective constructive criticism. 




> A vial of lentiviral vectors I have created is sitting somewhere close and I’m arguing to either intradermally inject them or not. This vial of lentiviral vectors can potentially (with a high probability) bring my hair back at the site of injection. I already had AAV antigens, so couldn’t use them. I’ve developed a lentiviral system using a bi-cistronic expression of shRNA and a catalytically dead CRISPIR (CRISPRi) both targeting AR in a VSV-G-pseudotyped replication-deficient lentivirus. This can silence AR probably up to 99% for a couple of years or more but can also *cause cancer, with a low probability, but that can happen.* There is almost a zero chance for the virus to go systemic. My lentiviral genes are under strong promoters and these promoters can sit in wrong places when integration happen and purely out of murphy's law cause cancer. You guys probably have absolutely no idea what I wrote here but that's the current state of affairs.


 Assume that I am an idiot and explain in simple terms how your lentiviral can cause cancer? Also, there are capillaries in the scalp sitting quite close to the skin, how will you avoid systemic exposure? Can we see some pictures of the equipment you're using to create your lentiviral vectors? (This is so that people stop questioning your competency and credibility). What you're talking about is pretty revolutionary so I suggest you take this a bit more seriously (I cant tell if you are). Moreover its wrong of you to say most people wont understand what youre saying, not everyone has a degree in biochem so it'd be nice if you could help us lay folk understand what you're doing without relying on "its too complicated to simplify". Otherwise you might be better off talking to yourself...

----------


## FGF11

> Assume that I am an idiot and explain in simple terms how your lentiviral can cause cancer? Also, there are capillaries in the scalp sitting quite close to the skin, how will you avoid systemic exposure? Can we see some pictures of the equipment you're using to create your lentiviral vectors? (This is so that people stop questioning your competency and credibility). What you're talking about is pretty revolutionary so I suggest you take this a bit more seriously (I cant tell if you are). Moreover its wrong of you to say most people wont understand what youre saying, not everyone has a degree in biochem so it'd be nice if you could help us lay folk understand what you're doing without relying on "its too complicated to simplify". Otherwise you might be better off talking to yourself...


 
You're not an idiot, it's just that I don't have the energy to explain everything. Lentiviral integration is pretty random (tendency to happen in transcriptionally active genes), so it can cause clonal expansion by sitting behind oncogenes and activating them through positional effect. Promoters are very complex, imagine a CMV promoter in a lentiviral vector, it can go and turn on other genes as well as that gene it's supposed to turn on.

----------


## joachim

> You're not an idiot, it's just that I don't have the energy to explain everything. Lentiviral integration is pretty random (tendency to happen in transcriptionally active genes), so it can cause clonal expansion by sitting behind oncogenes and activating them through positional effect. Promoters are very complex, imagine a CMV promoter in a lentiviral vector, it can go and turn on other genes as well as that gene it's supposed to turn on.


 
hi fgf11, is there a safer alternative to what you're doing or what could be the next step now? if you know that it can cause cancer, then don't continue.
but wasn't it your intention from the beginning to create that virus? you knew the risk of cancer from the beginning, no?
so if it's to dangerous to try it means the end of the road... or do you have other ideas to proceed?

----------


## Boldy

Hi FGF11,

thanks for your sharing man, and taking the time to post it, it looks like you are familiar with the journals at-least, however for someone who is so deeply involved in such a trial in practice, it would be very very easy to provide some kind of photo graphic evidence of the"process" right?. we had allot people coming and going with just claims on this forum. Not saying you are one of them, but just to prove your point. You said you are a fan of open  science, well sharing details would be part of open science right?

I look  forward to your answer. I am happy to discuss your protocol after your post.

----------


## jjo

hey FGF11, how's it going? i come here very often to see if you have anything new to say.  Hope your ok

----------


## UNBEAT

> hey FGF11, how's it going? i come here very often to see if you have anything new to say.  Hope your ok


 +1

----------


## breakbot

I believe this guy has something to say.
I don't think he is a troll or something and he has a logical theory on AGA.
I don't know if you succeed but i hope so..Any information FGF11?

----------


## jjo

> I believe this guy has something to say.
> I don't think he is a troll or something and he has a logical theory on AGA.
> I don't know if you succeed but i hope so..Any information FGF11?


 I believe in him as well. maybe he discovers something only time will tell but i give him all the credit in the world for really trying.
I wish i could be in touch with him through email, i've tried to make contact on this site but i guess private messages are not possible.

----------


## silver

i'm very interested in this thread as well, FGF11 seems very smart and motivated... I hope the negative jerks from here didn't make him leave.
Many of us are waiting if you have something to say.

thanks

----------


## fred970

> i'm very interested in this thread as well, FGF11 seems very smart and motivated... I hope the negative jerks from here didn't make him leave.
> Many of us are waiting if you have something to say.
> 
> thanks


 Sorry, I've ruined our last hope for a cure, if only I didn't make fun of FGF11/Dr. Nigam, baldness would have been cured!

----------


## paleocapa89

It's one thing to unmask scammers and mock them, and another thing to attack everyone who want's to do something about hair loss - especially when he made proof of solid scientific knowledge -  and pollute every topic with negativity and cynicism. I don't know whether FGF11 will drive the collective knowledge of hair loss forward, but I'm pretty sure your contribution won't.

----------


## fred970

> It's one thing to unmask scammers and mock them, and another thing to attack everyone who want's to do something about hair loss - especially when he made proof of solid scientific knowledge -  and pollute every topic with negativity and cynicism. I don't know whether FGF11 will drive the collective knowledge of hair loss forward, but I'm pretty sure your contribution won't.


 29 pages. Proof? Where?

----------


## jamesst11

Most giant discoveries in science aren't just made over night by one person... they are from an accumulation of knowledge contributed to by many scientists and even just smart individuals.  I am happy we have people of all capacities and resources exploring this, it needs to happen more.  Proof or no proof, this makes me happy.

----------


## Link Mahboi

> Most giant discoveries in science aren't just made over night by one person... they are from an accumulation of knowledge contributed to by many scientists and even just smart individuals.  I am happy we have people of all capacities and resources exploring this, it needs to happen more.  Proof or no proof, this makes me happy.


 Wish I could upvote this

----------


## PatientlyWaiting

> Most giant discoveries in science aren't just made over night by one person... they are from an accumulation of knowledge contributed to by many scientists and even just smart individuals.  I am happy we have people of all capacities and resources exploring this, it needs to happen more.  Proof or no proof, this makes me happy.


 Very true. In 1916 Albert Einstein predicted that we would get ripples in space in his General Theory of Relativity. This is caused by two black holes clashing and merging and then warping time and space around it, the fabric of space, 1.3 billion light years away. And when this happens, gravitational waves are sent through space. Now in February 2016, his prediction came true and we finally identified these gravitational waves, of an event that happened before even dinosaurs were around. Why did we do it now, because we needed much better technology to find these waves in space. 

It was kind of off topic, but it shows what you said that something can't be done over night by one person is very true and it applies to all science fields, even one of the most intelligent beings in History. It had to be done by many many scientists over the course of multiple decades. Now don't get me wrong I don't want it to take 100 more years, hopefully it doesn't take until the year 2116 to get a hair loss cure lol. But I agree with your post.

----------


## Dimoxynil

a cure for me is to beat nature, which is not happening any time soon. But if we could trick it somehow ?

----------


## UNBEAT

any update??

----------


## jjo

> any update??


 
+ 1
is everything ok FGF11?

----------


## Tobias

I don´t know if the thread starter is still following this thread. But lets try. 

According to your theory, it is important to not only prevent the androgen-AR-interaction but also androgen independent AR activation (translocation into the nucleus). Therefore one has to either make the AR disappear altogether (like you tried to) or induce a permanent loss of intranuclear function of the androgen receptor. There are hundreds of known mutations that cause androgen insensitivity. A few of them will not only affect the androgen-AR-interaction but also to intranuclear affinity of the AR to its target. 
What do you think of inducing such a point mutation via chimeric DNA/RNA oligonucleotids? The site directed mutations could be induced ex situ by extracting the hair follicles in order to prevent systemic side effects.

----------


## Tobias

I don´t know if the thread starter is still following this thread. But lets try. 

According to your theory, it is important to not only prevent the androgen-AR-interaction but also androgen independent AR activation (translocation into the nucleus). Therefore one has to either make the AR disappear altogether (like you tried to) or induce a permanent loss of intranuclear function of the androgen receptor. There are hundreds of known mutations that cause androgen insensitivity. A few of them will not only affect the androgen-AR-interaction but also to intranuclear affinity of the AR to its target. 
What do you think of inducing such a point mutation via chimeric DNA/RNA oligonucleotids? The site directed mutations could be induced ex situ by extracting the hair follicles in order to prevent systemic side effects.

----------


## Tobias

Forgot to say: the idea of fgf11 is not far fetched at all and far from being a scam. If you believe that finasteride works, then you have to believe that his idea works. He just takes it a step further. His approach is not some magical snake oil but an approach that researches use daily to investigate the role of all kinds of proteins in in vitro experiments. 
This forum is a mixture of all kinds of people from different backgrounds. His motivation most propably was: I have a good idea but not the time or resources to develop it on a bigger scale so I at least want it to be a stepping stone for someone who really works in this field.

----------


## silver

I hope fgf11 is still involved here, I would love some more info and update.

take care fgf11, post soon

----------


## UNBEAT

WHATS your idea TOBIAS?can you share with us so we can discuss about it?
You can make a new thread about this

----------


## jjo

FGF11 i really hope this thread doesn't die, any news to report?

----------


## Link Mahboi

Did he try to inject the stuff on his head after all?

----------


## UNBEAT

> Did he try to inject the stuff on his head after all?


 +1

----------


## Hairmore

FGF11 probably killed himself with some experimental treatment. Poor guy.

----------


## Link Mahboi

> FGF11 probably killed himself with some experimental treatment. Poor guy.


 Cancer is a bitch, but I didn't know it could act that fast..

----------


## bej

> #1 - Finasteride nor any androgen based therapy is going to regrow the amount of hair possible with Minoxidil. As already mentioned, castration only stops hair loss... it doesn't act as ultimate regrowth.
> #2 - If dermarolling is extremely uncomfortable you are doing it wrong. It does not have to be as aggressive as some people make it.
> #3 - You have not followed the long term dermarolling progress. PrettyFly83 went from a NW6 to almost a NW3. In this study men on Finasteride AND Minox for 2-5 years were at a stand still and started regrowing more hair after adding dermarolling:
> http://www.ncbi.nlm.nih.gov/pubmed/26120151
> 
> Everyone on this forum is far underestimating it because of dumbasses like fred. No one is doing long term runs with the correct supplements for skin support (MSM / Vitamin C / Zinc).


 I was reading through the paper, linked above, an Indian dermaneedling study. These kind of studies usually look very promising, but I almost always find strange details that make me wonder what's going on.

Look at the photos of the treatment. Specifically, Figure 5 shows Patient 1 at 6 months. Then look at Figure 7 (which has 3 photos) of Patient 3 at 6 months. The upper-right picture in Figure 7 is THE SAME as the one picture in Figure 5. WTF? I could see this from the thumbnail size, and when you look at the photos up close, you can clearly see they used the same photo for 2 different patients. Either they faked the results, or they have real results, but are so sloppy and careless that they used the same photo twice. I'm very careful with my research and I don't understand how someone could make such a mistake in a publication like that, and then nobody in the lab even catches the mistake.

----------


## bej

If/When FGF11 comes back, I'd like to ask him, can he give us the sequence of the oligo he made?

----------


## fred970



----------


## bej

> If/When FGF11 comes back, I'd like to ask him, can he give us the sequence of the oligo he made?


 When I typed that, I hadn't got to the part where FGF11 says he's starting up a company. I'm still not done catching up with the thread, but here's my thoughts:

I found it odd that he dismissed every other strategy, yet was so confident about his own. His strategy is to target 1 gene with a gene silencing technique. I'm not sure what level of knock-down he could achieve, but often the genes aren't completely knocked down by these kinds of techniques. And if I assume he aspires to something more than the black market, this is going to require FDA approval for him to sell it. Given that MPB is cosmetic purpose, I highly doubt the FDA would approve a medicine that is injecting a virus into your scalp to alter gene expression. And that's assuming the technology even works. Here's me playing devil's advocate. The virus is foreign to your body. Although it won't be replicating like an infection, your body might still be able to "detect" the "infected" cells. For all FGF11 knows, people might get one of these treatments and have their immune system destroy all the hair follicles. Especially with repeated treatments, each time your immune system will get better and better at detecting and destroying cells expressing foreign proteins.

And I keep thinking back to the fact this is just for 1 gene. An important gene, but still just one gene. It's not likely to be a cure. And it's going to be very very expensive. You'd have to go to a special clinic, and the people there would need to have the expertise to handle these custom viruses, etc.

This thing is going nowhere. Best case scenario, it's available in 10 years.

----------


## iaskdumbquestions

Just bumping this in case someone has heard something. FGF said he wrote this, so he can find people to talk about this intellectually with. Maybe he, chemical, swooping and others have become part of an underground cure AGA mission. 

But seriously FGF, if you see this can you give us an update.

----------


## iaskdumbquestions

Just bumping this in case someone has heard something. FGF said he wrote this, so he can find people to talk about this intellectually with. Maybe he, chemical, swooping and others have become part of an underground cure AGA mission. 

But seriously FGF, if you see this can you give us an update.

----------


## jjo

> Just bumping this in case someone has heard something. FGF said he wrote this, so he can find people to talk about this intellectually with. Maybe he, chemical, swooping and others have become part of an underground cure AGA mission. 
> 
> But seriously FGF, if you see this can you give us an update.


 +1
Would love an update or contact soon.

----------


## cichlidfort

> *Hi Fred970* I was thinking whether I should do this or not, many times when I did a google search, some of these forums showed up. So I just created an account to share what I did. Now, I did what I needed to do, share my knowledge and findings.  Hope it shows up in some google search of someone. Please remember this, I said many times that this is not a complete treatment (or cure). It needs injections [you can't do that to your whole temples, all the time], It is ridiculously expensive, and it might have side effects when done in bigger scale. Also, if you call being employed in one of the most scientifically advanced places in the world, basement. I have nothing further to add. * This is the last post I have in this forum or any other forum on the web, the only other place I mentioned this was a blog.* Sincerely.


 You just wrote a novel about nothing. GTFO!

----------


## fred970

> You just wrote a novel about nothing. GTFO!


 I warned everyone here but apparently I was the idiot.

Don't trust random people on a f-ing message forum.

----------


## jjo

> I warned everyone here but apparently I was the idiot.
> 
> Don't trust random people on a f-ing message forum.


 it's because of dinks like you he's gone.. if you don't agree or don't have anything good to report in the thread then piss off

hope he comes back

----------


## fred970

> it's because of dinks like you he's gone..


 Oh please!

----------


## Iron

I hope he comes back

If he doesn't it's only because it didn't workout.. His protocol is very cutting edge you know

----------


## UNBEAT

HEY guys, FGF11 has spread his knowledge to us.Now we know when it consist, what is needed for to produce , how to produce it .
And now that we know all this can we make and try it ourselves?
what do you think

----------


## jjo

> HEY guys, FGF11 has spread his knowledge to us.Now we know when it consist, what is needed for to produce , how to produce it .
> And now that we know all this can we make and try it ourselves?
> what do you think


 really? your going to try this?

----------


## bej

I'm a molecular biologist, and what FGF11 says he did is beyond the scope of what you can do on your own. Plus, he left out critical details, like the specific DNA sequence he used. Plus, there's no proof, just some text from a random stranger on a hair loss site. There's nothing to see here, except nothing going nowhere.

----------


## jjo

really FGF11, your not coming back?

with all respect, if your gone because some people here are idiots then maybe you could toughen up a little and get back in the game.
If it's another reason then that's ok but we still hope you come back.

----------


## Cartech78

Hey bej , this is a link from a hairloss 2020 there is a discussion started by a guy name Roman about 3a-HSD enzymes being a diamond in the ruff , you have any input, thanks 
http://www.hairlosscure2020.com/incr...comment-100913

----------


## iaskdumbquestions

> I'm a molecular biologist, and what FGF11 says he did is beyond the scope of what you can do on your own. Plus, he left out critical details, like the specific DNA sequence he used. Plus, there's no proof, just some text from a random stranger on a hair loss site. There's nothing to see here, except nothing going nowhere.


 Since you're a molecular biologist why can't u cure hairloss?

Thanks.

P.S. look at me username before responding

----------


## Trouse5858

The arrogance of the title of this thread never ceases to amuse me.

----------


## rbrown

> The arrogance of the title of this thread never ceases to amuse me.


 It is desperation more than arrogance. People have been claiming the same for thousand of years.

http://www.forbes.com/sites/sarahhed.../#31833a9f295b

----------


## robodoc

He is not arrogant.  He is young and learning.  If a thousand PhD's can't figure AGA I doubt this guy can but hats off for making an effort.  He is a college student so cut him some slack.  Some here seem to complain if a person comments and fails to solve baldnerss....yikes, tough crowd I would say.

----------


## Anton5redA

Hi FGF11, this question is for you:
This is off-topic of antisense oligonucleatide injections but would you please give me an opinion about my trans-dermal delivery vehicle for Tofacitinib Citrate. 
I am currently using 50% Ethanol, 20% water, 20% phosphatidylcholine micelles (liposomes) and 10% propylene glycol by volume. 
I rub it all in pretty well, but believe that there is plenty of room for improvement of delivery. 
How about perforating stratum corneum a little with 0.5-0.8 mm dermastamping once a week then hold off the application of Tofacitinib for a day after? How much do you think that increases the transdermal delivery in the couple of days following the perforation?
I would rather not use the dermastamper and just use a reliable vehicle of course.

----------


## Cartech78

Fgf11 has been gone since he made this post ,

----------


## Anton5redA

Thank you for the heads-up. 
If anyone has any idea on which vehicle would work best for the permeation of scalp. 
I know that antifungal medications are used as topical ointments on all outer surfaces of the body except for the nails and the scalp, for which tablets must be taken to provide the necessary delivery to target tissues. So sad that the scalp is apparently as tough as nails for medications to penetrate. TOUGH AS NAILS ...

----------


## robodoc

Yea, I am not sure if he believed what he wrote or enjoyed being complex and wrong.  A little knowledge can be dangerous.  Thans for your critique.

----------


## Littlesadeyes

@fgf11 I am so in awe of and grateful for the research you have done here. I read your post and suddenly it all made sense when you explained it. Switch of the castration resistant AR splice variant.
Genius! I am so desperate to talk to you more about this but I see you have been inactive for quite some time here, but I thought Id give this a shot anyway. Im trying to figure out a way to edit the AR gene using a CRISPR to cut the splice variant you originally targeted with your ASO out. Id love your advice and perhaps collaboration on this endeavour because your brain CLEARLY is invaluable. If you read this, please know that what you have done here is appreciated. Hopefully I hear from you!

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## Ahab

> Fgf11 has been gone since he made this post ,


 I think he's bored with us and is instead now jerking everybody's chain making up conspiracy theories while calling himself Q.

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## Notgivingup2

Haha I remember commenting on this when it first popped up. Mindless dribble then and still is now. Love that people still buy into it.

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## Littlesadeyes

Mindless drivel if youre a pleb who doesnt understand what hes talking about. Bye.

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## Ahab

The OP spouts nonsense. The truth is that the weight of fat and skin below head level, weighs upon and pulls down on the skin going across the top of the head. This results in poor blood circulation which makes your follicles go to sleep--like when your foot goes asleep--and while asleep, they are prone to being clogged with dandruff, dust, and oil. This explains why there are so many fat bald men around, because the more body fat, the more the skin is weighed down. It also explains why so many bald heads shine--it's because the scalp is stretched so tight. This is how minoxidil works--derived from a low blood pressure medication, minoxidil improves blood flow to the scalp.

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## Ahab

> There are a lot of big problems in this world, that hair loss, sometimes seems actually quite small compared to them. Watch The Boy Whose Skin Fell Off, and  My Flesh and Blood  just to get an idea of how a disease such as Epidermolysis bullosa can be soooooooooo much worse than hair loss.


 Not worse. Only just as bad.

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## Beta Catenin

Well, where do I start this. I've been investigating on my own i I've come to exactly the same conclusions as you did, maybe with a different path.

There are a lot of comunication pathways within and outside the cells, so it becomes really hard to create a distinction between causality and correlation even harder to identify the most important underlying mechanisms in any pathology. You can act on hair loss in a million different ways, and still observe some results because of this, but only a few are truly effective and worth the money, time and side effects.

Lets start with DHT. DHT is old school known to be the androgenic ligand with most affinity with androgen receptors, which means it can act on AR even in small concentration in comparison with other androgens and maybe produce a bigger expression on the target genes. However, I too believe DHT is not the main mechanism here. DHT mediated AR activation upregulates the TGF beta pathway resulting in the productions of cytokins like the mentioned and a particularly small protein called Dkk1. Dickkopf 1 however is an agonist of the Wnt/B catenin pathway by contributing to the degradation of a transcription coregulator Beta Catenin. Reduced cytoplasmic levels of Beta catenin downregulate the Wnt canonical pathway and thus inhibiting its expression and the production of  IGF's. So that means DHT favours TGF pathway which in turn produces an Wnt/B cat antagonist (negative feedback).
As a result, the anagen phase becomes progressively shorter as a result of the smaller and smaller availability of Beta cat and growth factors, leading to the miniaturization of the hair folicles. Thats pretty much it for the main mechanism, or at least one of them (I doubt there are).

Why is it the main mechanism? Because of what i said before. There are hundreds of studies regarding hundreds of substances and methods, from natural antioxidants, herbs, teas, to mechanical stimulation. There are a multitude of factors that can impact the hair follicles and pretty much everything in our body, but its important to not lose valuable time and money on treatments that only produce small marginal benefits. As an example, DHT is related to an increase of reactive oxygen substances (free radicals for simplicty) which in turn might cause DNA damage, and as a response when detected DNA damage cells usually respond by producing tumor antigens and even induce apoptose. One of the proteins produced is the p53 that downregulates B catenin and consequently halting the cells growth. Therefore, antiox present in some extracts might benefit the follicles but only to a limited extend. Early onset of AGA is also associated with prediabetes or insuline resistance. Would a low glycemic diet promote hair growth then? Probably not, since insuline hormones are involved in a cascade of interactions regulation the active transport of gluscose into the cell which is partially mediated by the activation of Wnt signalling proving the insuline resistance (the fact cells cant properly uptake the right amounts of glucose) is not the cause but maybe the consequence of a faulty/susceptible Wnt/B catenin signalling. Mechanical stimulation is another example. The signalling from the epidermis to the dermal papillae can affect the composition of the matrix and influence the behavior of the surrounding cells; BMP, JAK-STAT, etc but so far everything I've seen is connected to the wnt pathway or the benefits are supressed when DHT is added (meaning DHT action mechanism is more preponderant for the condition). 

So, and why does DHT has a degrading effect on frontal hair and a positive effect on the development of beard, pubic hair, etc? (the famous androgen paradox)
Well, thats a though question. I cant say for sure, but if I would have to guess I would say the scalp hair must be of a different nature of have key morphological differences regarding body hair. And the same goes for eyelashes. Informally, we can see babies start to develop hair soon after they are born. Slowly vellus hair develop into intermediate and terminal hairs without the need of DHT, however, body hair follicles are also present since the day we are born but only develop after the adolescence in response to DHT. In my opinion, this paradox is a bit of misconception since were comparing two concepts similar at glance, but with completely different working mechanisms.

Some other thought i would like to add is that hair loss is probably trigger right after the puberty but because of the genetic predisposition of the androgen receptor density/ affinity, some people bald earlier, some people later; at some extends faster, sometimes slower but the clock starts at puberty for everyone. But why does hair loss not halt/slow down when we get older?
Thats true we lose 2% of free DHT/year if im not mistaken after 25yo but like ive said its not the only factor at play. As we grow older we start to suffer from other pathologies that indirectly may harm our hair, we start to suffer the consequences from oxidative and replicative senescence, increasing the apoptosis rates amongst cells and white hairs.

I believe the ultimate cause is a genetic polymorphism in the genes which code the androgen receptor, but I think its pretty much what most people think anyway. However, targeting the AR with inhibitors its the most effective way to address AGA, but its also the worst in terms of side effects AND does not equate to regrowth in late stages. So what i propose is to address the cytoplasmic beta catenin by inhibit among all available targets the Dkk1 in special since its the one upregulated (and the others have other functions and are important tumour suppressors).

So what about regrowth? I asked myself the same questions. If erasing DHT from the equation wasnt enough to revert hair loss then, I assumed 2 central possibilities: there is a more important mechanism than DHT, which i think its impossible because androgens are a must in AGA OR there are other AR activators which arent androgens but that sounded very unlikely too until i found an article about castration resistent prostate cancers too. It makes total sense. If you look at balding patterns, they are always the same. There is a great variation regarding balding duration (20-80) but not so much regarding patterns (comparing to other alopecias). If all follicles were equally sensitive, then because the scalp DHT levels shouldn't fluctuate so much between regions, the extension of the binding reacting should in theory not be enough to cause a "local" balding but instead the balding spots should be evenly distributed (or definitely more distributed and less centered). Thats why I think the immunological response and macrophage/ cytokins population of the inter cellular tissue is a key aspect in the pattern shape and why inflammation plays such a crucial role in balding.

So just like previously by activating the Wnt pathway you could stop hair loss, you can also induce hair growth! (theoretically) 

Just an example, lets analyze a popular regimen on hair loss talk hormonal route consisting of Cyproterone Acetate, duta and estradiol gel. The first solely is a potent androgen inhibitor, which would prove effective if the goal was only halting the hairloss (depending on the concentrations ofc), duta (not a anti androgen per se) but the regrowth is only possible thanks to the topical estradiol. Estradiol is a potent androgenic antagonist and within the cell, it acts opposite to DHT and inhibits TGF, Dkk1 and activates Wnt by stabilizing beta catenin.

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## Ahab

> The OP spouts nonsense. The truth is that the weight of fat and skin below head level, weighs upon and pulls down on the skin going across the top of the head. This results in poor blood circulation which makes your follicles go to sleep--like when your foot goes asleep--and while asleep, they are prone to being clogged with dandruff, dust, and oil. This explains why there are so many fat bald men around, because the more body fat, the more the skin is weighed down. It also explains why so many bald heads shine--it's because the scalp is stretched so tight. This is how minoxidil works--derived from a low blood pressure medication, minoxidil improves blood flow to the scalp.


 So why when people have hair transplants doesn't the fat keep pulling the skin tight and make the transplants go to sleep?

And why do some fat people have plenty of hair while some skinny people go bald?

And why don't women go bald on the tops of their heads like men?

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## Beta Catenin

Im not very well educated in hair transplants.

Fat people usually have low androgens. I dont know if you know that DHT also binds to AR in adipoctytes and stop the production of "fatness". Why do women are less muscular than men and have more fat tissue? Short answer, because they have a lot less circulating androgens than men also hence then rarely go bald, just get thinner hair most of the times.

But black or white, fat or skinny it doesnt really matter. You can have normal DHT and still suffer the consequences if you have an abnormal AR expression, which imo is most cases. And even if you reduce but not completely erase DHT from your system, cells can adapt either at receptor level, lowering the treshold of required androgens for activation, or also at transcription level, 1 gene instead of producing 1 protein produces 2 or 3. Its too complex.

Your follicles dont go to "sleep" because of the lack of blood flow. Most of blood flow acts as a termoregulator anyway, cells could live with a portion of it. For that matter mechanical stimulation/microneedling/hot temperatures would produce amazing results, which they dont. At most it has a minor effect on hair loss, it's not even close the main mechanism. Also and maybe more importantly, the partial pressure of circulating oxygen in scalp is also decreased which might favour the expression of some potential proteins. I haven't ruled out that hypothesis but havent investigated it properly either.

The thing is, there are a million treatments which produce mild results. You could spend a fortune to get shity results, or you could target directly the adequate mechanisms

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## Ahab

> The OP spouts nonsense. The truth is that the weight of fat and skin below head level, weighs upon and pulls down on the skin going across the top of the head. This results in poor blood circulation which makes your follicles go to sleep--like when your foot goes asleep--and while asleep, they are prone to being clogged with dandruff, dust, and oil. This explains why there are so many fat bald men around, because the more body fat, the more the skin is weighed down. It also explains why so many bald heads shine--it's because the scalp is stretched so tight. This is how minoxidil works--derived from a low blood pressure medication, minoxidil improves blood flow to the scalp.


 I just realized something: I didn't post #331. WTF?

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## Aminar

Your theory is exciting but did you tried to test it with a more scientific approach?
I recommend talking with some professors maybe they can help you to develop your theory and even publish a peer-reviewed article.

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## sayian

> Well, where do I start this. I've been investigating on my own i I've come to exactly the same conclusions as you did, maybe with a different path.
> 
> There are a lot of comunication pathways within and outside the cells, so it becomes really hard to create a distinction between causality and correlation even harder to identify the most important underlying mechanisms in any pathology. You can act on hair loss in a million different ways, and still observe some results because of this, but only a few are truly effective and worth the money, time and side effects.
> 
> Lets start with DHT. DHT is old school known to be the androgenic ligand with most affinity with androgen receptors, which means it can act on AR even in small concentration in comparison with other androgens and maybe produce a bigger expression on the target genes. However, I too believe DHT is not the main mechanism here. DHT mediated AR activation upregulates the TGF beta pathway resulting in the productions of cytokins like the mentioned and a particularly small protein called Dkk1. Dickkopf 1 however is an agonist of the Wnt/B catenin pathway by contributing to the degradation of a transcription coregulator Beta Catenin. Reduced cytoplasmic levels of Beta catenin downregulate the Wnt canonical pathway and thus inhibiting its expression and the production of  IGF's. So that means DHT favours TGF pathway which in turn produces an Wnt/B cat antagonist (negative feedback).
> As a result, the anagen phase becomes progressively shorter as a result of the smaller and smaller availability of Beta cat and growth factors, leading to the miniaturization of the hair folicles. Thats pretty much it for the main mechanism, or at least one of them (I doubt there are).
> 
> Why is it the main mechanism? Because of what i said before. There are hundreds of studies regarding hundreds of substances and methods, from natural antioxidants, herbs, teas, to mechanical stimulation. There are a multitude of factors that can impact the hair follicles and pretty much everything in our body, but its important to not lose valuable time and money on treatments that only produce small marginal benefits. As an example, DHT is related to an increase of reactive oxygen substances (free radicals for simplicty) which in turn might cause DNA damage, and as a response when detected DNA damage cells usually respond by producing tumor antigens and even induce apoptose. One of the proteins produced is the p53 that downregulates B catenin and consequently halting the cells growth. Therefore, antiox present in some extracts might benefit the follicles but only to a limited extend. Early onset of AGA is also associated with prediabetes or insuline resistance. Would a low glycemic diet promote hair growth then? Probably not, since insuline hormones are involved in a cascade of interactions regulation the active transport of gluscose into the cell which is partially mediated by the activation of Wnt signalling proving the insuline resistance (the fact cells cant properly uptake the right amounts of glucose) is not the cause but maybe the consequence of a faulty/susceptible Wnt/B catenin signalling. Mechanical stimulation is another example. The signalling from the epidermis to the dermal papillae can affect the composition of the matrix and influence the behavior of the surrounding cells; BMP, JAK-STAT, etc but so far everything I've seen is connected to the wnt pathway or the benefits are supressed when DHT is added (meaning DHT action mechanism is more preponderant for the condition). 
> 
> ...


 Absolutely

IMPRESSIVE

Everything you wrote here In the last 10 years  I researched. I have the same conclusion


GET this data somehow to Japan to replicel dudes that work for the people, because BIG PHARMA will ignore such info as they push minoxidil propecia finasteride posions that do nothing to the people.

Come on surely slowly we are finding the cure and fixing this baldness problematic gene once and for all for full hairs ! spread the message

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## sayian

Bro ... any sign of life ?

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## AmyChrister

Hi. Thank you for your honest experience and I am sure others will also appreciate it. I am just curious whether I'll get the same results if I repeat the same things as you.

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