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 Show JAK Inhibitors Work for Alopecia Areata

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.”