Category Archives: JAK Inhibitors

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 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.

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”:

More Good News on JAK Inhibitors for AA; Mixed News on JAK Inhibitors for AGA

I was 50/50 about writing an entire post on JAK inhibitors, but in the end gave in due to the fact that I usually neglect the 1-2 percent of balding people who suffer from alopecia areata (AA) or the related conditions alopecia totalis and alopecia universalis.  For a majority of these people, JAK inhibitors clearly seem to be a cure assuming there are no long-term side effects.

There are also some new developments in the more controversial JAK inhibitors for androgenetic alopecia (AGA) patients discussion that are worth elaborating.  As is the norm when JAK related news comes out, the discussion in the prior post was taken over by this subject, in no small part due to “nasa_rs”.   I have let him run rampant in the comments section only because he came back after a lengthy break from this blog.  He will be allowed to continue posting the same stuff in the comments to this post, but thereafter I will become stricter.  It should be noted that despite his often repetitive comments, over the years “nasa_rs” has sent me some highly interesting and unique scientific information.  And recently, he was the first one out there to find the good news about Alcaris Therapeutics adding JAK inhibitor trials for AGA patients to their website’s pipeline page.  As a side note, if I recall, “nasa_rs” really did or does work for NASA…a bit of a scary thought.

Two New Studies Support JAK Inhibitors Working on Alopecia Areata (AA) Patients

In 2014, two groundbreaking papers discussed complete reversal of hair loss in alopecia areata patients.  While this was justifiably by far the biggest news of the year in the hair loss world (and widely covered by the global media due to the spectacular before and after patient scalp photos), there was one problem: the first of these two studies only involved one patient of Dr. Brett King (on arthritis drug tofacitinib), and the second only involved three patients of Dr. Angela Christiano (all three on bone marrow cancer drug ruxolitinib).

Two weeks ago, two new larger studies were released that solidified the above findings:

  1. Dr. Angela Christiano’s team from Columbia University in New York found that 75 percent of 12 patients with alopecia areata had successful hair regrowth while on ruxolitinib for between 3-6 months followed by a 3 month follow-up period.  By the end of treatment, average hair regrowth was 92 percent.  Perhaps the best part of the news: “The drug was well-tolerated in all participants, with no serious adverse events.”
  2. Even more significant, a much larger joint study from Stanford University (led by Dr. Anthony Oro) and Yale University (led by Dr. Brett King) found that of 66 alopecia areata patients treated with tofacitinib, 64 percent of patients had a positive response to treatment (and 32 percent achieved an improvement of over 50 percent after only 3 months of therapy). Side effects were generally mild.

From the above studies, it seems like ruxolitinib is better than tofacitinib when it comes to treating alopecia areata.  It remains to be see if results are even better when treatment is continued for a longer duration when it comes to either of the above two drugs. Note that a number of other newer JAK inhibitors will get approved and come onto the market in the US in the coming years.

Finally, for those who do suffer from alopecia areata, this is by far the best place in the internet to connect with others such as yourself.

JAK Inhibitors for Androgenetic Alopecia (AGA)

Some good news, some bad news and some in-between news here.

The Good:

  • First, from the 12 patient study article link I posted in the above section, Dr. Christiano still seems optimistic about JAK inhibitors working for AGA per the following quote:

“The CUMC research team plans to expand their studies to include testing these drugs in other conditions such as vitiligo, scarring alopecias, and androgenetic alopecia (pattern baldness) where they may also show efficacy. “We expect JAK inhibitors to have widespread utility across many forms of hair loss based on their mechanism of action in both the hair follicle and immune cells,” said Dr. Christiano.

The Bad:

  • However, Dr. King who in the past thought that it was worth testing JAK inhibitors (especially topical ones) for AGA now seems pessimistic according to this article:

“King said it is doubtful that Xeljanz (=tofacitinib) will work for the most common types of hair loss (such as male pattern baldness), which are not the result of an autoimmune disease.”

Note that both Dr. Christiano and Dr. King are listed as advisers to Alcaris Therapeutics in the conflict of interest section of the earlier linked 66 patient study summary page.

The In-Between:

  • One important bit of information on JAKs and AGA that never received the attention it should have (partly because I did not cover this subject much in recent months) happened a few months ago when Solomon interviewed Dr. Eddie Wang (who previously worked with Dr. Angela Christiano).  According to Solomon, Dr. Wang “rated JAKs success chance for AGA 5 out of 10“.  Dr. Wang seemed to think that JAKs could be reducing microinflammation in AGA patients and that could help hair growth.  I contacted him about how he came up with this 5/10 estimate, but he never responded.  I would put this development under “good news” if Dr. Wang had responded with a detailed answer.

Two (or More) Variants of AGA?

I have mentioned in the past that it seems like a majority of balding people have significant itching and dandruff in their balding regions, while some balding people have none of those annoyances whatsoever.  I always wonder if the people who have this itching and dandruff associated with their balding also have a significant inflammation (and maybe even autoimmune) component to their hair loss?  If topical JAK inhibitors do end up helping people with AGA, will those with significant itching benefit more?  I would not at all be surprised if researchers some day find that AGA patients can be broadly split into two main camps.

Pharmacologic Inhibition of JAK-STAT Signaling Promotes Hair Growth

Finally, while I discussed this October 2015 study on this blog before as part of a lengthy post, I keep finding new items of interest in there.  I therefore thought it was worth pointing out the study again here in the hopes that some of the readers with a scientific background can give us more feedback on the contents.  Dr. Angela Christiano and Dr. Claire Higgins are both co-authors of this study. Some of the more interesting quotes:

“Hair growth after JAK-STAT inhibition mimics normal anagen initiation by activating the Wnt (Note: this is what Samumed is focusing on) and Shh signaling pathways.”

“JAK-STAT inhibition causes activation of hair follicle (HF) progenitor cells.”  (Note: also see this important patent filed in 2013: “Jak inhibitors for activation of epidermal stem cell populations”).

“Inhibition of JAK-STAT signaling improves skeletal muscle regeneration in aged mice.”

“Tofacitinib treatment promotes inductivity of dermal papilla (DP).”

“In human hair follicle assays, we show that JAK inhibition via tofacitinib treatment increases the growth rate of anagen hair shafts (skin grafts and organotypic culture assays) and enhances the inductivity of human DP spheres (neogenesis assays).  It is surprising that ruxolitinib treatment did not improve the inductivity of human DP spheres, despite the fact that it increased the rate of growth in the organ culture model. We postulate that down-regulation of proapoptotic signals in tofacitinib-treated spheres, which did not occur in ruxolitinib-treated spheres, may promote survival of DP cells, leading to enhanced hair growth in this assay.”