Big New Genome Wide Association Study On Androgenetic Alopecia - Preprint

[Nadia1972]

I use DMSO + castor oil, but I do not find it's strong enough. I think the TCA would be more appropriate to do a wounding.
My sebum is not too much in quantity but too thick.I think most people who have an Androgenetic Alopecia suffer from the same problem to varying degrees .What is bizarre is that dermatos say it is not the same disease whereas in both cases sebum comes into play
It is necessary to use mechanical means to clean the pores of the scalp while awaiting a gene therapy which will treat to the cause the problem of the quality of the sebum
Even a gene therapy that works half-way would quite suit me

 

[Grasshüpfer]

Here we go:

CRISPR gene-editing tested in a person for the first time
http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988


PD-1 Knockout Engineered T Cells for Castration Resistant Prostate Cancer
https://www.clinicaltrials.gov/ct2/show/NCT02867345?term=crispr&rank=2

 

[hellouser]

"The move by Chinese scientists could spark a biomedical duel between China and the United States."

Trump better have a response to that if he wants to continue his 'winning' narrative and China taking USA to the cleaners.

 

[Beowulf]

Here we go:

CRISPR gene-editing tested in a person for the first time
http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988

Yeah I saw that. We should make a different thread to speculate about it.

 

[InBeforeTheCure]

Theoretically that sounds like a perfectly good explanation of A.G.A. At this stage it seems like the only real way to prove the mechanism would be with 3D printed skin. But from what I've read dermal papilla cells do not divide, rather when the dermal papilla rises up to the bulge, the dermal papilla cells communicate to the epithelial cells through Wnt signalling to replenish the dermal papilla cells and then start to regrow the follicle (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115771/).

According to Olsen 2003 during miniturisation the dermal papilla gets smaller and smaller, suggesting that hair follicle size depends on the number of dermal papilla cells. Further Cotsarelis found that only CD34hi and CD200hiITGAS6 were missing in balding areas, yet KRT15hiITGAS6hi was still present (and the implication I've gotten so far is that it can make the CD200hiITGAS6 cells)

https://www.ncbi.nlm.nih.gov/pubmed/15617565

Yes, DP cell number and volume controls hair follicle size, but at the same time if you destroy a bunch of DPCs and then stop, the DP can fully recover (in mice) as long as the follicle can get back into anagen.

DP cell depletion in mice causes the changes in hair follicle structure and cycling that characterize progressive alopecia in humans, including reduction in both hair and follicle size, a prolonged telogen phase and an ultimate failure to produce new terminal hairs (Kligman, 1988). The selective reduction of the secondary germ region observed in these mice as an indirect consequence of DP cell depletion is also observed in androgenetic alopecia in humans (Garza et al., 2011). In this context, it is noteworthy that when the underlying cause of DP cell depletion is removed in our mouse model, the follicle exhibits an intrinsic capacity for regulative regeneration to produce normal hairs, but only when DP cell number is sufficient to stimulate anagen re-entry.

(Chi et al., 2013)

It wouldn't be a huge stretch to infer that the same could be true in humans. If you cut a follicle below the bulge and transplant either the top part (containing the bulge) or the bottom part (containing the dermal papilla), either half will regenerate an entire follicle more often than not (Toscani et al., 2009). Also, in alopecia areata, T-cells attack and destroy both dermal papilla cells and dermal sheath cells (I think), as well as epithelial bulb cells, while the bulge is spared, and of course follicles in alopecia areata can grow back.

Some evidence that loss of epithelial bulge stem cells can drive HF miniaturization comes from a study done on HF aging. In aging loss of Krt15+ stem cells in the bulge results in HF miniaturization (Matsumura et al, 2016). Perhaps then signals (such as Sonic Hedgehog) from transit amplifying cells, which are derived from the bulge stem/progenitor cells, may control DP size. Of course, A.G.A. is a bit different in that Krt15+ stem cells are retained as you say, but CD200+ and CD34+ progenitor cells are profoundly depleted, but the end result on the DP would be the same. It would be interesting to know which signals are involved in stem -> progenitor cell conversion, but there hasn't been any work done on that AFAIK. It could include Wnt signaling though.

If signalling between the dermal papilla and bulge was diminished then the dermal papilla cells would have no way to proliferate, the less dermal papilla cells the less of an ability they have to communicate with the bulge to create more cells.

That would also explain DHT inhibition regrowth. Suddenly the DP can communicate with the bulge again and send a signal for more cells before it dies. It also explains how SM04554 works since it's a B-Catenin Agonist. It must tell the bulge to create more dermal papilla cells.

I don't know enough about minoxidil to factor that in, but I don't think anyone really does.



Oh yeah, and I can't believe how insidious AR is, I mean could it upregulate it's own gene? That would be crazy!

It could go either way. Sometimes DHT upregulates AR expression, sometimes it downregulates it. It depends on the cell type and so on.

Oh okay so by looking at our DNA they found a way to predict who would and who wouldn't have balding with 82% accuracy. So to increase the accuracy you could consider the actual connection between the genes, and look for potential SNP/Genes which they just might not have considered.

Does that mean we all have general Wnt signalling problems?

That's probably a part of it, but could and likely does involve other things.

But it does imply that there is an innate issue with our genome which is causing us to lose hair.

Thanks for the chapter, I think I'm starting to get this stuff now. Before I just kept searching the genes you mentioned in my uni's database and didn't get anything.

Good, good, glad it was helpful.

 

[InBeforeTheCure]

When I read these interesting thoughts, I ever think in sebum

Now what a surprise that is.

"When I read these interesting thoughts, I think of sebum."
"When I read any paper on hair loss, I think of sebum."
"When I wash my car, I think of sebum." - Armando Jose

Of course, the Kitagawa paper and the Leiros paper look at crosstalk between AR and beta-catenin (the crosstalk that was the inspiration for those "interesting thoughts") in co-culture systems and observed the effects on keratinocyte proliferation and stem cell function. Their co-culture system did not include sebum or sebocytes, so there's no need to resort to sebum theory to explain crosstalk between AR and Wnt signaling.

 

[Nadia1972]

It is the sebum that kills the hair follicles in the Androgenetic Alopecia. The scalp is engorged with sebum. Even if one wakes up the stem cells, nothing will happen with a scalp paralyzed by the sebum

 

[InBeforeTheCure]

It is the sebum that kills the hair follicles in the Androgenetic Alopecia. The scalp is engorged with sebum. Even if one wakes up the stem cells, nothing will happen with a scalp paralyzed by the sebum

So it's the sebum that kills the hair follicles in A.G.A. And the evidence for this is...?

 

[Nadia1972]

So it's the sebum that kills the hair follicles in A.G.A. And the evidence for this is...?

Nothing better in science than the experimental method rather than theory which comes out anywhere.I check it for almost 30 years.When my scalp produces more sebum because of sports or heat, my hair falls much more.It is even the hecatombe except since my hormonal treatment

 

[InBeforeTheCure]

Nothing better in science than the experimental method rather than theory which comes out anywhere.I check it for almost 30 years.When my scalp produces more sebum because of sports or heat, my hair falls much more.It is even the hecatombe except since my hormonal treatment

I'm pretty sure unfalsifiable anecdotes aren't part of the scientific method.

 

[Armando Jose]

I'm pretty sure unfalsifiable anecdotes aren't part of the scientific method.

Falsifiability has become an important part of scientific research
https://www.quora.com/What-are-some...ific-theories-that-are-not-falsifiable-if-any

BTW

"When I read these interesting thoughts, I think of sebum."
"When I read any paper on hair loss, I think of sebum."
"When I wash my car, I think of sebum." - Armando Jose

You are right, it is rare the day that I am not thinking about sebum issues , a lot of years..... but honestly I
To this day I have not found anyone to throw me totally my ideas to the ground, what's more, I think the biggest critic with them is myself.

 

[Grasshüpfer]

I think the sebum is a factor. As well as inflammation.

But DP cells also die (go senescent) if you add dht to them in vitro.


So sebum is definitely not the primary cause.

 

[InBeforeTheCure]

You are right, it is rare the day that I am not thinking about sebum issues , a lot of years..... but honestly I
To this day I have not found anyone to throw me totally my ideas to the ground, what's more, I think the biggest critic with them is myself.

Seems to me that there are some dusty old threads around (such as this one) where many of your ideas are not only thrown to the ground, but stomped on, and then run over with a 40-ton truck over and over and over and over and over and over and over and over and over and over and over and over again.

 

[Armando Jose]

Debunked my idea that persons with dense and thick hair are less proned to develop common baldness?
Who and when?

Also I think that DHT exist in scalp hair in persons years before puberty, Do you agree?

I have no real proof about different genetic healthy hairs in scalp, Do you have any?

BTW, The post is from 2007, passimg the time and no a real cure for common hair loss, or even a preventive......, what is the f***?

 

[InBeforeTheCure]

Debunked my idea that persons with dense and thick hair are less proned to develop common baldness?
Who and when?

Also I think that DHT exist in scalp hair in persons years before puberty, Do you agree?

The more direct problems are these:

- Castrates have dramatically reduced sebum, but incredible hair. Why?
- Those with complete androgen insensitivity syndrome (AR loss of function) have no or very low sebum, but incredible hair. Why?
- Hair transplants stick around, despite being in the same area that "isn't in contact with an absorbent surface". Why?

Some predictions of the hypothesis which are questionable, to put it mildly:
- Take a group of guys from a similar genetic background. The ones with long hair are much less likely to start losing hair. Really?
- Diffuse hair transplants -- take FredTheBelgian for example. Your hypothesis predicts that he should lose all of his transplanted hair because it's so thin, does it not?

I have no real proof about different genetic healthy hairs in scalp, Do you have any?

You mean not a genetic difference, of course, but an epigenetic difference. There have been many studies examining differences in gene expression between bald frontal scalp and non-bald occipital scalp, or between DPCs from bald scalp and DPCs from non-bald scalp, but unfortunately none looking at pre-balding differences between the two. Just to be clear, you don't have a problem with the concept of positional information and reaction-diffusion and so on giving rise to epigenetically distinct regions in the skin, do you? Let's say someone were to look at gene expression differences in frontal vs. occipital scalp in 14-year-old kids, many of which will lose hair later in life. I'm curious -- what do you think the odds are that they'll find differences in gene expression?

BTW, The post is from 2007,

And as far as I can tell, it hasn't gotten any less wrong since then.

passimg the time and no a real cure for common hair loss, or even a preventive......, what is the f***?

For preventative, we do in fact have finasteride, dutasteride, and topical AR antagonists. And hopefully nine years from now, we'll have full restoration available thanks to our lord and savior, Dr. Takashi Tsuji.

 

[Beowulf]

nine years from now, we'll have full restoration available thanks to our lord and savior, Dr. Takashi Tsuji.

What makes you say nine years?

Release development 3 years + 2 years post trial release + 1 maybe 2 years delay + 2 years FDA + 1 year transplant doctors actually caring?

 

[Beowulf]

Then again there will be like 100,000 hair transplant patients per annum by 2020, and they only expect to serve 10,000 patients a year at first...

I really hope they get their sh*t together when it comes to meeting demand, because I think it's going to be much higher than they expect.

 

[Grasshüpfer]

Then again there will be like 100,000 hair transplant patients per annum by 2020, and they only expect to serve 10,000 patients a year at first...

I really hope they get their sh*t together when it comes to meeting demand, because I think it's going to be much higher than they expect.

Regarding Tsuji.. I doubt everyone will jump on it in the first years. It opens up the possibility of full restoration for everyone destined to be Norwood 5-7.

But for example Hellouser could have a normal hair transplant first, to get to nw1 as his status is still quite good. He would progress to Norwood 6 with some plugs sticking around eventually however. But once Tsuji is out he knows he can get Tsuji a few years later when the status is getting worse again.

Eventually every hair transplant will be Tsuji powered, as it is less invasive and carries lower risk.

 

[Beowulf]

Regarding Tsuji.. I doubt everyone will jump on it in the first years. It opens up the possibility of full restoration for everyone destined to be Norwood 5-7.

But for example Hellouser could have a normal hair transplant first, to get to nw1 as his status is still quite good. He would progress to Norwood 6 with some plugs sticking around eventually however. But once Tsuji is out he knows he can get Tsuji a few years later when the status is getting worse again.

Eventually every hair transplant will be Tsuji powered, as it is less invasive and carries lower risk.

And here I was hoping we'd all have a forum party in Japan where we'd all get to meet each other.

Plus from the interview it sounds like it's going to be a little while before they figure out how to Tsuji into scar tissue, so a hair transplant could hold you back a bit.

 

[InBeforeTheCure]

What makes you say nine years?

Release development 3 years + 2 years post trial release + 1 maybe 2 years delay + 2 years FDA + 1 year transplant doctors actually caring?

That thread I linked to was from nine years ago, so I was saying hopefully Tsuji delivers before another nine years has passed. The sooner the better.