I think I've hacked it

[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.

[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?

[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?

[Seuxin]

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

[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.

[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

[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.

[jamesst11]

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

[UNBEAT]

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

[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.

[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.

[UNBEAT]

any news from fgf11..

[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.

[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]

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.