Category Archives: Tofacitinib

So JAK Inhibitors Could yet Still Cure AGA?

After my relatively long break, I had a lengthy post planned for today, but need to delay it due to a potentially great new development.

Summary of the Recent Past

In 2014, the biggest news in the hair loss world involved two separate developments related to two different JAK inhibitors (Ruxolitinib and Tofacitinib — search for both on this blog’s “Categories” menu as there are numerous posts on them) curing alopecia areata.  While those developments were incredibly exciting and groundbreaking, unfortunately the vast majority (>95 percent) of balding men and women suffer from androgenic alopecia (AGA) rather than alopecia areata (AA).  However, in 2014, Dr. Brett King did suggest that there was a possibility that JAK inhibitors could also cure androgenic alopecia during his interview with Spencer Kobren. In my own analysis, I have always stated that for many androgen related hair loss sufferers, perhaps there is also an inflammatory component (hence the increased itching and dandruff) and such cases could benefit from JAK inhibitors.

Thereafter, there was no news on this potential cure for AGA for a while, until in 2015 the one and only Dr. Angela Christiano posted results (albeit in mice) that suggested that JAK inhibitors could treat androgenic alopecia.  A must read post.  Moreover, this could occur via a topical (as opposed to oral) formulation of the two main candidate drugs: Ruxolitinib and Tofacitinib!

Thereafter, silence yet again for a long time.  Even worse, Christopher1 on hairsite stated that JAK inhibitors did not cure his androgenic alopecia.  He seems like a very reliable forum member over there so I was disappointed. However, the one good thing is that we do not know how accurately people are using JAK inhibitors at the moment since some are using off-label products, some are going to inexperienced physicians, some are trying topical experiments etc… so I still had some hope.  In any event, please be aware of the risks involved in these experiments and do not try them yourself.  Always see a physician before trying any drug to treat hair loss.

Thereafter, further contributing to the bipolar disorder and mood swings, on March 5 2016, a commentator named “Rick” posted an interesting comment on this blog that was largely ignored (and I am very surprised at this).  Although I hate to trust any one such commentator (especially in this particular case since he is also using Minoxidil as part of his treatment), I will still paste his comment below since it was missed by so many blog readers:

Just want you all to know that I have had very good success. With using tofacitinib 30% mixed with minoxidil. I have been doing this process topically for 3 months and have achieved full follicle growth! I will update you more in 30 days. And yes that is for male pattern baldness.

Perhaps “nasa_rs” has influenced me too much and I am looking for any positive signs?

Today

In any event the whole reason for this post is that today came news that Aclaris Therapeutics was buying Vixen Pharmaceuticals (Dr. Angela Christiano and Columbia University affiliated company).  See Form 8-K here.  At first, when I read a one paragraph news alert summary of this acquisition, I did not think much of this development since I had been to Aclaris’ website in the past and remember reading that they only deal with Alopecia Areata related drugs.

However, I then read a lengthier article about this latest acquisition and some things (see below in red font) clearly stood out:

“As a result of this transaction, Aclaris acquired worldwide rights to intellectual property licensed to Vixen by Columbia University covering the use of certain Janus Kinase (JAK) inhibitor compounds for the treatment of alopecia areata, androgenetic alopecia and other dermatological conditions.”

“The acquisition of the Vixen intellectual property and the licensed JAKPharm and Key Organics compounds solidifies Aclaris’ presence in the JAK inhibitor space and allows us to broaden our focus in hair loss to include androgenetic alopecia, often referred to as female or male pattern baldness,” said Neal Walker, President and Chief Executive Officer of Aclaris. [HT: Commentator Julian for pointing out that Mr. Walker is also CEO of Follica].

“We are delighted to enter into this agreement with Aclaris for the development of JAK inhibitors for alopecia areata, androgenetic alopecia, and other hair loss disorders,” said Dr. Christiano.”

In conclusion, welcome back nasa_rs.

Ruxolitinib and Tofacitinib Could Also Regrow Hair in AGA

Last Year

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 100 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 1 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 that Spencer Kobren did 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

Lo and behold, today Dr. Angela Christiano and her team published some findings (FULL TEXT AVAILABLE) 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 (although it should be noted that they also grafted human hair onto the mice and achieved great results):

Image below from this Daily Mail article:

 

Ruxolitinib and Tofacitinib Hair Growth

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 1 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.