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.