JAK Inhibitors Show Great Potential as a Hair Loss Treatment

Angela Christiano is up to it again, and the online hair world is very thankful.

It was just a little over a year ago when the internet was ablaze with the news that Dr. Angela Christiano and her colleagues were studying the pharmaceutical drug ruxolitinib in cases of alopecia areata. Like tofacitinib, ruxolitinib is a type of drug known as a JAK inhibitor. First, the studies were done on mice and showed successful hair growth. Those studies were then followed up by a pilot trial involving 12 human subjects. The results from the human study were significant. As you can see, several subjects were able to regrow full heads of hair. That was pretty exciting news at the time, although, these results were found in cases of alopecia areata which is different and much less common than regular “pattern baldness.” Alopecia areata is an autoimmune disorder in which the immune system attacks hair follicles. Still, this study raised the question of whether JAL inhibitors could be helpful for those experiencing common hair loss.

Topical is the way to go

On October 25, 2015, Dr. Christiano and colleagues released the documentation of their latest research “Pharmacologic inhibition of JAK-STAT signaling promotes hair growth.” This time they were testing topical formulations of the JAK inhibiting drugs, tofacitinib and ruxolitinib, as a treatment for androgenic alopecia or “common” hair loss. The results of this recent study showed that topical applications were even more effective than the former study which involved oral administration of the drugs. There’s a lot of information dispersed throughout the multiple media articles which have been written, the scientific article published by Christiano & her peers, and the multiple videos which were released about this study. I’ve highlighted the proceeding facts to give the most insightful view of the implications of this research.

Many of the articles online have highlighted the trademark photograph of the three mice side by side demonstrating the hair growth effect of the JAK drugs. However, if you carefully examine the scientific article published by Christiano you will also notice these photos which depict human hair growing on human skin grafts which were placed onto the backs of mice.

Basic RGB

http://advances.sciencemag.org/content/1/9/e1500973.full


You will also notice the photos at the bottom titled “Human DP Spheres”. In these experiments, human dermal papilla cells were cultured in 3D environments and the JAK inhibitor drugs were added to the cultures to see what kind of effect they would have on the hair follicle growth process. Check out that tofacitinib photo, quite impressive. See “Joseph’s Thoughts” later in this article for a potential application of this treatment approach. Hint: Rapunzel.

Dr. Christiano mentions in one of the articles online that “The surprise was when we started using the drugs on alopecia areata patients, when we used them topically the hair grew back much faster and more robustly than it did orally.” That means that topical JAK inhibitors have already been tested on humans. Another article mentions at the bottom, “It remains to be seen if JAK inhibitors can reawaken hair follicles that have been suspended in a resting state because of androgenetic alopecia (which causes male and female pattern baldness) or other forms of hair loss. So far, all the experiments have been conducted in normal mice and human follicles. Experiments to address hair follicles affected by hair loss disorders are under way.” The wording of that paragraph leads me to believe that Dr. Chrisiano and colleagues may have begun pilot studies testing JAK inhibitors in humans with androgenic alopecia, which is of course, a good thing.

These fascinating JAK inhibitor drugs have a multi-faceted affect on hair follicles. Here are some descriptions of their methods of action from the published study:

JAK inhibitors stimulate hair follicles out of the resting phase into the growing phase. They also show the ability to elongate the growing phase.

JAK inhibitors activate the Wnt and Shh signaling pathway.

JAK inhibitors cause the activation of hair follicle progentior (stem) cells.

Tofacitinib (a JAK inhibitor) promotes inductivity of dermal papilla cells.

Tofacitinib promotes hair growth by positively affecting genes within pathways that are crucial to hair growth. For example: TGFB pathway genes, BMP pathway genes, LEF1, and NOTCH pathway genes.

As a bonus aside, the scientific study also depicts results from using a “Sonic Hedgehog” pathway agonist. It is listed as SAG and depicted in the study’s photos. The hair growth results from using SAG appear very good, but not quite as impressive as the JAK inhibitor drugs.

Joseph’s Thoughts

This is more of a curious thing, but I had to notice that Dr. Christiano is definitely marketing her hair research to the ladies. The latest barrage of articles mentions that Dr. Christiano has patented the use of JAK inhibitors for hair growth and will be commercializing them through her new company Vixen Pharmaceuticals, Inc. Earlier this year in a NY Times article it was mentioned that Dr. Christiano was also co-founding a company that is developing a cellular based treatment for hair regeneration using cultured hair follicle stem cells. The name of that company is Rapunzel. That would make two decidedly feminine aliases for her hair tech ventures. It’s fine with me as I am quite certain that the technology itself is applicable to both men and women.

How does this research relate to other hair growth treatments that are being developed right now? As I said in this article, topical is the way to go. If you thought it would be a good idea for Kythera Pharma to develop a topical version of Setipiprant at some point, this latest research definitely validates that sentiment. Today, I happened to revisit Cotsarelis’ research on PGD2r inhibitors and hair growth (the research that was essentially licensed to Kythera). I was reminded that he was using a topical version in his mice studies. Now, this latest JAK inhibitor study brings forth great evidence that topical delivery is the most effective method for growing hair.

Lastly, I want to thank Dr. Angela Christiano for her beautiful presence in the world of hair regeneration research. It’s very nice to watch her discuss her findings in some of the videos that have accompanied this latest development.

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