JAK-STAT Signaling Jump Starts the Hair Cycle

Over the past few years, I have discussed the janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway a number of times.  It has become of increasing importance in the hair loss world ever since JAK inhibitors were first shown to cure alopecia areata (AA) in 2014.  Even prior to that development, there had always been some interest in the JAK-STAT signaling pathway and its relationship to the hair follicle cycle.

However, since 2014, research in this area seems to have multiplied significantly.  In 2015, I discussed Dr. Angela Christiano, Dr. Claire Higgins et al’s groundbreaking paper titled “Pharmacologic inhibition of JAK-STAT signaling promotes hair growth“.

Now, in the latest (November 2016) issue of Journal of Investigative Dermatology, Columbia University’s Dr. Angela Christiano, Dr. Etienne Wang and Dr. Sivan Harel have published a new paper titled “JAK-STAT signaling jump starts the hair cycle“.  Thanks to the commentator in the last post who notified us about this.

However, it should be noted that this paper does not pertain to any new study or research by Dr. Christiano!  Instead, it is largely an analysis by the Columbia University team of a study/paper that was published earlier this year by Dr. Julien Legrand and his team at The University of Queensland.  This study from Australia was titled “STAT5 activation in the dermal papilla Is important for hair follicle growth phase Induction“.  The conclusion of that paper was that “STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling“.  STAT5 is an acronym for signal transducer and activator of transcription 5.

Dr. Christiano’s team raises some interesting points in there analysis, especially the fact that while Dr. Legrand’s research has shown that JAK/STAT5 signaling in the dermal papilla is required for
anagen onset in the murine (mice) hair cycle, other researchers have shown that JAK inhibition is able to induce the transition of telogen to anagen in wild-type mice.  This contradiction highlights the complexity  and still yet to be fully understood nature of JAK-STAT signaling in the various stem cell niches of the hair follicle.

Dr. Christiano continues to believe that topical JAK inhibitors could work to treat regular male pattern hair loss via the following quotes:

“Targeting the JAK-STAT pathway might be a potential treatment for nonimmune alopecias”.

“Further work in this exciting area may uncover novel pathways that control hair follicle stem cell quiescence and activation.  Targeting
these pathways pharmacologically may facilitate the discovery of new therapies to treat various forms of alopecia”.

“In our recent study (Note: its the one I mentioned earlier from 2015) we found that in wild-type mice, topical application (rather than systemic treatment) with JAK inhibitors was required to trigger the telogen-to-anagen transition, possibly due to a requirement for high threshold local concentrations of the drug in the hair follicle.  Further, we found that the timing of topical treatment was crucial: treatment induced hair growth only if administered after 8.5 weeks, during late telogen”.

Nothing groundbreaking in this development, but it seems like the University of Queensland based Australian team of researchers is important enough to warrant inclusion in my global map of hair loss research centers.  One of the co-authors (Dr. Kiarash Khosrotehrani) of their paper specifically mentions research interest in “hair follicle biology, cycling and regeneration” in his biography page.

FYI:  For the scientists amongst you that are interested, there is another paper in this same November 2016 issue of Journal of Investigative Dermatology titled: “Effects of Imiquimod on Hair Follicle Stem Cells and Hair Cycle Progression.”

Brief Items of Interest, October 2016

Hair loss news first:

Update: A day after I wrote this post, CNN covered JAK inhibitors in a new article (in a pleasant surprise, they also looked at the androgenetic alopecia — AGA — angle).  Usually, all these articles on JAK inhibitors only look at alopecia areata (AA).  Yet again, Dr. Christiano says she is optimistic that JAKs could work on AGA patients (but only in a topical form).  Dr. Brett King is not optimistic, but he is still testing it out (in a lotion form) on his AA patients (probably the ones who also have AGA).  In the above article, the one AA patient who they show with regrown hair after being on oral JAK inhibitors did not regrow hair that he lost to AGA, although it is impossible to tell whether he did not regrow 100 percent of his AGA hair loss or not.  In any event, we will only know for sure about this once they test topical JAK inhibitors out so people should not get so emotional about this subject each time there are new developments.  You should also not try to test your own topical version as even the experts are having a hard time developing the appropriate version.  According to Dr. Christiano:

“Though she thinks men might have the same success with an ointment, she said the trick is that it has to penetrate properly. Compared with the paper-thin skin of mice, human skin is “much thicker, and it’s oily, and it’s deep, and it’s got a fat layer — so there’s a lot to think about when making a good topical formula.”

It is well worth watching the video in the above article just to see the funky haired mice.

— In a first, myself as well as all of this blog’s commentators missed the important International Society of Hair Restoration Surgery (ISHRS)’s 24th Annual Congress that ran from September 28th through October 1st in Las Vegas.  I did not even see any threads on the conference in any of the hair loss forums out there, which is strange.  I usually cover the 2-3 most important hair loss related conferences in the world every year in separate posts, but this time I forgot to do so.  You can find the detailed ISHRS 24th Congress final program guide here.  As usual, there were way too many interesting presentations.  For our purposes, the most important ones were:

  • Dr. Angela Christiano: “JAK Inhibitors, Hair Regeneration and
    Genetic Testing”.
  • Dr. Pantelis Rompolas: “Potency and Contribution of Stem Cells to Hair Follicle Regeneration”.
  • Dr. Rodney Sinclair: “Advancing our Understanding of the Biology of Androgenetic Alopecia and Changing the way we use Minoxidil to Treat it”.
  • Dr. Angela Christiano and Dr. Ken Washenik led a discussion titled “Biotechnology in Hair Regeneration”.

On Twitter, Dr. Alan Bauman told me that while Dr. Christiano did not provide any data on JAK inhibitors for androgenetic alopecia (AGA), she did hint that JAK inhibitors seem to stimulate the anagen phase of the hair growth cycle.  Fingers crossed as usual when it comes to this subject.  I was surprised at the number of presentations on body hair transplants (BHT), with Dr. Arvind Poswal discussing long-term ten-year plus results of his BHT patients.  Also surprising were the number of presentations on platelet-rich plasma (PRP).

— In stark contrast to the above glaring omission, in the past week at least 10 (!) people either commented under a blog post or e-mailed me about cosmetics behemoth L’oréal (France) and Poietis (France) partnering to bioprint hair follicles via laser. This news item was extremely well covered across the global media and there are hundreds of articles on the internet about this interesting subject matter.  The end goal “holy grail” of this research will be to implant the new hair follicles into balding regions.  Below is the official company video outlining the technology and the goals behind this partnership:

— Unfortunately, it seems like Replicel has not fulfilled the contractual obligations of its partnership with Shiseido (although the former disputes this allegation).  In any event, it is unlikely that this will stop Shiseido from proceeding with its plans.

Cassiopeia (Italy) updates us on its topical anti-androgen product Breezula (formerly called CB-03-01).  Also see my past post on this subject.  It seems like even if phase 2 and phase 3 clinical trials succeed, this product will not come to market before 2021.

— Samumed’s Dr. Osman Kibar’s presentation (a small part of it is on hair loss) at a recent conference organized by the UK’s Royal Society of Medicine.  He received many compliments on Twitter for his presentation.

Cellmid has better than expected quarterly sales of its FGF5 inhibiting product Evolis in Australia.

Kerastem completes enrollment in Phase 2 clinical trials.

— Dr. Ken Williams and his government funded trials for injecting adipose derived stem cells (ADSC) into patient scalps to help hair growth.  You can still register for the trials if you are in the US.

Spex has a brand new updated website, which is worth a visit.

— Former baseball great Jose Canseco just announced today that he will get a hair transplant with Dr. Parsa Mohebi next week.

— Sportscaster Joe Buck’s hair transplant addiction nearly cost him his voice and his career.

The benefits of going bald.  I would much rather have none of those benefits and hair instead:-)

Men’s vanity involves hair transplants.

And now on to medical items of interest:

— The National Geographic is a highly reputable magazine so I believe them when they say that ending blindness is no longer just a dream.

Rapamycin could make your dog (and maybe humans too) live longer.

Microsoft aims to cure cancer in ten years.  In the end it is just a programming error.

— A very interesting new endeavor: “Human Cell Atlas project aims to map the human body’s 35 trillion cells“.

Teeth regeneration advances.

Building a bionic spine.

3D printing continues to revolutionize the field of prosthetic limbs.

First “three person baby” born in Mexico (doctors went there from the USA so as to escape strict regulations).  Baby’s parents were Jordanian.  Medicine will hopefully soon become very multinational.

Stem cells regenerate damaged monkey heart.

— Yet more evidence that turmeric is very good for you, but only when added to food that is then cooked.

Endurance training causes positive genetic changes.

— Not sure if I believe half the stuff in the below video, but it is well presented with 100 percent thumbs up likes thus far: K. Comella: “Reversing Aging with Stem Cells”:

Follica Updates its Website and it Looks Encouraging

As always, thanks to commentator “Mike” who regularly seems to find the latest developments with Follica immediately.  He notified us of the updated Follica website earlier today in a comment to the last post.

I have covered Follica (a subsidiary of US-based PureTech Health) many time on this blog before in spite of the fact that until recently I was very skeptical about the company (since it was founded ten years ago, but has yet to commercialize its skin perturbation + topical compound technology despite years or supportive evidence). Moreover, some people on hair loss forums have over the years postulated that the company’s technology is basically just glorified Minoxidil, since skin damage allows for greater penetration of Minoxidil.  However, the company has never specified what compound it is using, and I highly doubt it is just Minoxidil.  In some of their patents they have mentioned various potential ingredients including Minoxidil, but I am too lazy to go through all the links in my past Follica posts at the moment to get the details.

I bolded the words “until recently” above because a few months ago, Follica pleasantly surprised us and announced that it was aiming for a 2018 product release as a best-case scenario.

Now it seems like Follica just made a major upgrade to its previously barren website.  Nothing really of major surprise in there, but much better elaboration of the technology with useful photos/product renditions.  We already knew that the skin disruption process (which requires great precision and knowhow) would be undertaken at a doctor’s office and the compound application would be the responsibility of the patient at his or her home.  Now Follica has provided images of both the in-office and at-home devices.  The company will have a smartphone app to monitor progress (Edit: It seems like the app will also be able to measure the accuracy of your dosage via wirelessly communicating with the at-home device).

No information is provided about the costs, but they do discuss re-ordering of the compound, which makes me wonder if this will be a lifelong commitment just like with Minoxidil?  Assuming that you do get new hair follicles, how susceptible will they be to the ravages of dihydrotestosterone (DHT), and will taking Finasteride or Dutasteride to reduce DHT levels prevent the need for re-ordering Follica’s compound?

Some key quotes from Follica’s new website:

“We’ve teamed up with leading dermatologists with expertise in hair loss and epithelial stem cell biology to develop a new system aimed at not just improving existing hair growth, but also growing new hair”.

“Our technology is based on a proprietary approach intended to create an “embryonic window” in adult skin, allowing new follicles and new hair to form from epithelial stem cells”.

“Following skin disruption, cells that migrate to help healing are forced to make a decision: Should I make epidermis, or should I make a hair? There is a window of opportunity in which we can potentially push them to choose the latter, and we believe there are multiple biological pathways to target to enhance this outcome. This regenerative effect is called hair follicle neogenesis”.

Dr. George Cotsarelis and his own Hair Loss

Finally, if anyone lives near where Dr. George Cotsarelis (Follica’s co-founder and technology inventor) works in Pennsylvania, it would be good to know if the small bald patch on the back of his head is gone or still there. To see what I mean, check out the below video links that start in the most relevant places. I am very serious and do not mean to belittle Dr. Cotsarelis (and hope he does not mind), but I feel like most people who can fill back a small bald patch on their crown region would always do so if they had the technology at their disposal. Usually, only those who totally shave their heads are comfortable with their hair loss, while those with small bald spots are not.  Maybe I am being too judgmental here and Dr. Cotsarelis does not care about his minor hair loss at all?  But if he were to suddenly have thick hair at the top/rear of his scalp, I would get even more excited about Follica.

Dr. Cotsarelis has been involved in hair loss research for at least 20 years as far as I can tell, and there is no-one in the world who has been cited in hair loss related magazine articles as much as him.  For those who are interested, in some of my past blog posts about Follica, I have discussed and linked to various wounding related patents and studies attributed at least in part to Dr. Cotsarelis.

Link to Dr. Cotsarelis Video 1

Link to Dr. Cotsarelis Video 2

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