I think I've hacked it - BaldTruthTalk.com
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  1. #1
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    Default I think I've hacked it

    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 (letís call them dormant), are activated by a signal (testosterone and DHT) to produce hair shaft and grow (just like mammary glands). Itís 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.

    Itís 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 donít 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 donít 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 donít 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 donít 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 donít 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 itís impossible as of now to know the signals.

    I donít 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 wonít. Itís 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.

  2. #2
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    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.

  3. #3
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    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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    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, itís 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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    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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    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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    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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    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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    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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    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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