How JAK Inhibitor Hair Loss Treatments Were Discovered

The American Hair Research Society (AHRS) is currently holding its annual American Hair Research Summit which is on until 16th May 2018 in Orlando, Florida.

One of the key talks being given is by Paul Changelian, Ph.D., the Vice President of Biology at Aclaris Therapeutics, Inc. - a company at the forefront of current hair loss developments.

Tofacitinib (Xeljanz) being trialled as Alopecia Areata TreatmentThrough the company's work with scientists from Columbia University in New York, and its acquiring a portfolio of exclusive patent licenses, it is one of the major players in the field of Janus kinase (JAK) inhibition as a potential treatment for various hair loss conditions. Those involved hope that this suite of drugs will produce the first MHRA licensed and FDA approved treatment for severe forms of Alopecia Areata, though they are also being explored in relation to Androgenetic Alopecia.

What are JAK inhibitors?

Initially conceived to reduce organ transplant rejection, JAK inhibitor drugs target Janus kinase enzymes.

Named after the two-faced Roman god of beginnings and endings, Janus kinase enzymes effectively act as an on and off switch for a number of cellular functions. There are four JAK proteins - JAK1, JAK2, JAK3 and TYK2 - which are involved in this signalling, using something known as the JAK-STAT pathway.

The JAK-STAT pathway is effectively a chain through which messages are passed down to cells via signalling proteins (cytokines) which control immune and inflammatory responses, among other functions. In the same way as a message may become mangled during a game of Chinese Whispers, when any part of this pathway is faulty, health issues may arise. JAK1 and JAK3 in particular are thought to be linked to the development of dermatological autoimmune diseases.

Where JAK inhibitors come in, is to target certain proteins and block the relevant cytokines which may disrupt faulty signalling preventing the mechanisms that then produce disorders such as psoriasis and Alopecia Areata.

It is hoped that by using this suite of drugs, hair loss - especially from Alopecia Totalis and Alopecia Universalis which currently have no effective or proven treatments - can be successfully managed, and hair regrowth may then occur.

Development of JAK inhibitor hair loss treatment

Today Dr. Changelian is giving a talk entitled “Preclinical to Clinical Translation of JAK Kinase Inhibitors", during which he explored the history of JAK inhibitor drug development.

Dr. Changelian is a former Pfizer scientist who then joined Confluence Life Sciences, Inc., a company founded by former Pfizer scientists. It was during his time at the pharmaceutical titan that he became known for his role in discovering and subsequently developing the first JAK inhibitor, tofacitinib. This process took seven years and the resulting drug which is used in the treatment of the autoimmune disorder, rheumatoid arthritis, goes by the Pfizer brand name of Xeljanz.
Arthritis Drug Tofacitinib Used to Treat Hair Loss from Alopecia Universalis Images taken of the patient during the initial 8-month trial using tofacitinib (Xeljanz) to treat plaque psoriasis and Alopecia Universalis at Yale University

It was the first JAK inhibitor approved by the USA's Food and Drug Administration (FDA) for treating autoimmune disease, though many have doubts about its serious side effect profile which includes an increased risk of tuberculosis, among other health issues. It is for this reason that the UK's equivalent of the FDA, the MHRA, has not granted the drug a licence.

As part of its stated commitment to developing JAK inhibition to treat various hairloss conditions, Aclaris Therapeutics acquired Confluence Life Sciences in 2017, which was when Dr. Changelian joined the company.

It gradually became clear that JAK inhibitors had a potentially wider scope of application with regards autoimmune disease and oncology, with one of the cellular functions they were able to influence being hair growth.

In 2014 researchers at America's prestigious ivy league college, Yale University, found whilst using Xeljanz as an exploratory treatment on a patient with plaque psoriasis and Alopecia Universalis - both autoimmune disorders - that it had the ability to regrow hair. Alopecia Universalis is the most acute form of autoimmune alopecia, causing the entire body to become hairless from head to toe. Yet, despite this, the patient - a 25 year old man who had been completely bald for seven years - regrew his scalp, facial and body hair whilst on an 8 month course of tofacitinib citrate.  This hair growth was a side-effect of taking the drug in 10mg doses per day for two months, then in 15mg daily doses for three months, in order to treat his psoriasis, for which it was only deemed 'mildly effective'.

Since then fellow Ivy League institution, Columbia University has taken on extensive research and development of JAK inhibitor hair loss treatments. In addition to tofacitinib, they have developed ruxoltinib and baricitinib which they are still investigating for the treatment of both autoimmune and genetic hair loss. Both topical and oral formulations of JAK inhibitor treatments are being produced and trialled; it is likely that this is because applying a drug topically can help to reduce the number of associated potential side-effects.

Should you wait for JAK inhibitors to start hair loss treatment?

According to a press release regarding Dr. Changelian's lecture, he believes that 'Harnessing the benefits of JAK inhibition for dermatological conditions will require minimizing the potential for over suppression of the immune system and subsequent infections, through strategies such as identifying molecules highly selective for JAK1 and JAK3 inhibition or developing topical formulations with high skin permeability while minimizing systemic absorption'.

Whilst a long development process, with the initial anticipated date of JAK inhibitor hair loss treatments being made available for prescription being 2021, it is an extremely exciting area of development - especially for people who have previously had no options for regrowing hair.

Belgravia specialists are often asked if it's worth hanging on for JAK inhibitors before seeing hair restoration help. For conditions which are currently untreatable, the answer is yes given there are no appropriate alternatives as yet. For adults with the scalp-only form of Alopecia Areata, or for those experiencing Male or Female Pattern Baldness, however, hair loss treatments are already available.

The hair may regrow naturally within 12 months in the case of mild Alopecia Areata so seeking treatment immediately is not so much of a priority. But, in cases of hereditary hairloss, these are permanent, progressive conditions so rather than waiting for the next best thing to be released, it is best to take action as soon as possible using courses featuring clinically-proven medications. Then - if desired - should any new wave of treatments prove promising and receive the necessary MHRA licence and FDA approval in the future, a switch can be made, but some positive changes should at least have become noticeable, helping to stabilise hair fall, promote regrowth and prevent baldness in the meantime.

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The Belgravia Centre

The Belgravia Centre is a world-renowned group of a hair loss clinic in Central London, UK. If you are worried about hair loss you can arrange a free consultation with a hair loss expert or complete our Online Consultation from anywhere in the world for home-use treatment.

View our Hair Loss Success Stories, which includes the world's largest gallery of hair growth photos and demonstrates the level of success that so many of Belgravia's patients achieve.

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