Study Explores Relevance of JAK-STAT Pathway to Genetic Hair Loss

Following the success of investigations into the JAK-STAT pathway and its involvement in autoimmune disorders, researchers at Cairo University in Egypt are exploring its potential links to genetic hair loss.

Trial registration data published on the website suggests that the trial will start on 15th October 2018, with an estimated end date of 1st April 2019.

What is the JAK-STAT pathway?

Put simply, the JAK-STAT pathway is an evolutionarily conserved signaling chain through which proteins in cells communicate. Its normal functioning is crucial for ensuring the stability of many biological processes including growth and the immune system.

"It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease (Xing et al., 2014). However, whether this pathway plays a role in other hair loss disorders remains unclear," says the Cairo University team.

The Egypt-based team states in its clinical trial registration that the aim of the study is to assess STAT3 levels in participants with Male Pattern Baldness. "We hypothesize that STAT3 levels will be elevated (due to a previous study proving that JAK-STAT pathway is involved in non-immune mediated hair loss in mice (Sivan et al., 2015))," they write.

Exploring the links between Male Pattern Baldness and the JAK-STAT pathway is likely to produce findings that are also applicable to Female Pattern Hair Loss - the women's equivalent of this genetic condition. However, further studies would be needed to confirm this, especially seeing as the retrospective, punch biopsy-based research will feature just 25 participants, making it small in scale. Continues below...

Key Steps of the JAK STAT Pathway diagram

Likely implications for Male Pattern Baldness and Female Pattern Hair Loss

Currently the understanding of how these hair loss conditions occur is that people inherit a genetic predisposition towards male/female pattern baldness which can come via a number of different genes that can be inherited from either or both sides of their family. When this predisposition is active it causes them to develop a sensitivity to the hormone dihydrotestosterone (DHT) any time following puberty. It can, however, remain dormant meaning no outward signs of hair loss develop but the relevant genetics can still be passed on - this is why the condition can be seen to skip generations.
How DHT Shrinks Hair Follicles How DHT Shrinks Hair Follicles aka Hair or Follicular Miniaturisation

In both men and women with genetic hair loss the susceptible areas are located along the top of the scalp, from the crown to the hairline, and the temples. As DHT binds to follicles in these areas it weakens them, causing them to produce increasingly weaker, thinning hair or - particularly in men - a receding hairline, and eventual hair loss. Though this may result in baldness in men, women tend to experience advanced thinning but rarely go completely bald.

Knowing more about the exact biological processes involved in androgenetic and androgenic alopecia, including any relating to the JAK-STAT pathway can only be helpful. Particularly for the exploration and development of new treatments for hair loss.

A number of JAK inhibitor hair loss treatments, initially developed as treatments for the autoimmune disorders Alopecia Areata, Alopecia Totalis and Alopecia Universalis, have already had patents issued in relation to treating male and female pattern hair loss too. There are various trials planned or underway investigating their use as novel genetic hair loss treatments, and further information as to how these are progressing is expected over the next year. With the first JAK inhibitor treatments for Alopecia Areata expected to be finalised and licensed/approved in time for a 2022 release, it is likely JAK inhibitors for male and female pattern baldness may not be too far behind.

In the meantime, given these hereditary conditions are permanent and get worse over time, it is generally advised that anyone wishing to stabilise shedding, promote regrowth and prevent baldness, takes advice in a timely manner. Clinically-proven hair loss treatments are already well-established and recognised by medical regulatory bodies, with the key topical and oral medications for genetic hair loss being both MHRA licensed and FDA approved.

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