Last Year: Ruxolitinib and Tofacitinib for Alopecia Areata

Last year, by far the biggest news of the year involved two likely cures for alopecia areata (AA) in humans. One was the arthritis drug tocafitinib and the other was the cancer drug ruxolitinib. Both drugs are classified as Janus kinase (JAK) inhibitors, and it is likely that many other drugs from this family will lead to similar results when it comes to hair regrowth. If you read my two main posts on this subject from last year (see here and here), it should be quite obvious how exciting the news was based on the large-scale global media coverage at the time (and of course the miraculous before and after human scalp photos instead of the usual mice photos).

Unfortunately, the vast majority of men (and many women too) who have hair loss suffer from androgenic alopecia, also known as male pattern baldness (MPB). There are probably at least 50 times as many people who suffer from MPB as there are who suffer from alopecia areata. So the big news of last year was only useful to 2 percent of hair loss sufferers, at least for the time being.

While many people (including the famous Dr. George Cotsarelis) dismissed the potential for JAK inhibitors to work on people who have androgenic alopecia, I was not so pessimistic. In my posts from last year, I mentioned that MPB probably also had an immune system attack/inflammatory component to it (and JAK inhibitors seem to cure alopecia areata via stopping the immune system from attacking the follicles). My theory was partly due to the fact that I and numerous others get a lot of itching and dandruff while losing hair (especially if not using shampoos such as Nizoral).

I was therefore very surprised that Dr. Cotsarelis was dismissing these developments so fast. It should be noted that all of his decades of work and numerous patents could go down the drain if JAK inhibitors were to cure MPB in humans without any major side effects, since this is one rare area of hair loss research that Dr. Cotsarelis has never touched.

Strangely enough, the two teams that discovered the cure for alopecia areata last year were both based in New York. One was led by Dr. Angela Christiano and the other was led by Dr. Brett King. The latter has credited the former with being the pioneer in this work.

My biggest reason for keeping faith in the potential of JAK inhibitors to also work on people with male pattern hair loss was the Bald Truth interview with Dr. Brett King. In the video, Dr. King mentions that a topical formulation of Tofacitinib would likely be tested on patients with Androgenic Alopecia. He clearly felt that JAK inhibitors could perhaps work on MPB patients too.

If I had to rate the chances of a hair loss cure for MPB arising from JAK inhibitors after that interview from last year, I would have said 3/10. After the below groundbreaking developments of today, I will raise my rating to 5/10. The one big issue is whether these drugs can regrow hair that has been lost for more than several years. Also an issue is long-term side effects, but so far the oral JAK inhibitors do not seem to have caused any deaths. And the topical version of those inhibitors will likely lead to even fewer side effects.

Today: Ruxolitinib and Tofacitinib for Androgenetic Alopecia

Lo and behold, today Dr. Angela Christiano and her team published some findings that suggest a better than negligible chance of JAK inhibitors also working to treat androgenic alopecia. This time, they managed to grow hair on rats via a topical formulation of both Ruxolitinib and Tofacitinib. Below are the stunning pictures, albeit in mice this time. However, it should be noted that they also grafted human hair onto the mice and achieved great results.

Image below from this Daily Mail article:

Some key quotes from Dr. Christiano per various articles from today:

“Male pattern hair loss follicles are stuck in the same state where these drugs seem to work.”

“What we’ve found is promising, though we haven’t yet shown it is effective for male pattern baldness.”

“JAK inhibitors seem to be among the very few number of compounds that produce hair growth very soon after their application.”

“But applying such drugs topically would be far safer.”

“Delivering it on the skin also seems to get more of the drug into the hair follicles.”

“Some topical agents induce tufts of hair here and there after a few weeks, but very few have such a powerful and rapid-acting effect.”

JAK Inhibitors Might Directly Affect Hair Follicles

The most interesting part of these experiments was that the mice grew more hair when the drug was applied topically to their skin versus when it was given to them to take internally. The research team thinks that this implies that JAK inhibitors might have a direct effect on hair follicles, in addition to the already known effect of inhibiting the immune attack. It should be noted that the precise terminology for this whole mechanism is “pharmacological inhibition of the JAK-STAT pathway/signaling”, with the STAT standing for “signal transducer and activator of transcription .”

JAK Inhibitors and Dermal Papilla Cells

I also found it interesting that the full published study has the following quote in the Abstract:

“We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae.”

A huge amount of hair loss research entails dermal papilla cells. I am not a scientist, but it seems like the above findings could also have ramifications for companies involved in 3D culturing of dermal papilla cells. In fact one of the co-authors of today’s groundbreaking paper is renowned hair loss researcher Dr. Claire Higgins, who has done quite a bit of work on 3D culturing of dermal papilla cells.

Vixen Pharmaceuticals

According to the NBC article on this development:

“Columbia University has filed patent applications relating to the discoveries reported in this paper, which are being commercialized through Vixen Pharmaceuticals, Inc., of which Dr. Christiano is a founder.”

This is interesting since some months ago I mentioned the fact that Dr. Christiano was supposedly starting a new company named “Rapunzel”. Perhaps she will have two companies devoted to curing hair loss: one for pharmaceuticals and one for work related to hair cloning and hair multiplication (i.e., cell culturing, stem cells etc…)?

I find this development encouraging since it makes more sense for Dr. Christiano to start a company devoted to this treatment only if she feels there could be at least some benefit to people suffering from MPB. Otherwise, she only has a market of at most 2 percent of balding people who have alopecia areata. And even that market would be split with other companies and doctors such as Dr. King that might make their own topical version of a different JAK inhibitor.

Videos

— The video from CBS does not embed very well in correct size, but is worth watching.

— Also see the video from Columbia University.