New research published in the journal PLOS Biology is sending ripples of excitement through the medical and trichology communities. Our Chief Science Officer, Jacky van Driel, gives her appraisal of the data available.
Titles used in media outlets are very eye-catching, such as: “Osteoporosis Drug Could Produce New Baldness Treatment” or “Baldness Cure Could Come From Side-effect Of Cancer Drug”, but what can we expect from these new findings?
Let’s break down what the research is about:
- After accidentally finding out that Cyclosporine A (CsA), an immunosuppressant cancer drug, induced unwanted hair growth, scientists at Manchester University, found the mechanism behind this hypertrichosis: CsA happened to reduce the activity of a protein called secreted frizzled-related protein 1 (SFRP1). SFRP1 is an inhibitor of the anagen phase.
- CsA has too many undesirable and dangerous side effects, so it couldn’t be use efficaciously for treating hair loss, but the scientists now had a new pathway they could investigate: what if SFRP1 could be inhibited? Could hair then continue its normal growth cycle?
“This inspired us to design a new pharmacological approach that uses WAY-316606, a reportedly well-tolerated and specific antagonist of SFRP1, to prolong the growth phase of the hair cycle.”
- This is where WAY-316606 makes an appearance, as it is an antagonist of SFRP1 activity.
- Researchers at Manchester University used donated human hair follicles ex vivo (“out of the living” in Latin, but not necessarily in a petri dish, which would be “in vitro”) and observed successful results.
Further reading can be found here http://www.manchester.ac.uk/discover/news/fringe-benefits-drug-side-effects-could-treat-human-hair-loss/
The questions that immediately spring to mind are:
- Would this also work in vivo (“within the living)? Basically, would it work on us humans?
- When will this be ready?
- Is it safe? Safer than Cyclosporine A? safer than Minoxidil, Finasteride and Dutasteride?
- How much will it cost?
- Will the financial, medical, and psychological price to pay for maintaining/regrowing our hair be worth it?
We will have to wait and see once some rigorous clinical trials have been completed. This could be many years. As with other hair loss drugs, if this does make it into the market it will almost certainly be classified as a medicine, so the safety of the product will need to be very well understood, including all possible side effects. The following scientific background is helpful to fully understand the article.
- We all know about the hair growth cycle: anagen (growing phase), catagen (transition phase) and telogen (resting/quiescence phase).
- It’s been observed that in the resting phase, the Wnt proteins/β–catenin in the outer bulge cells target a gene called Axin2, which is constantly expressed throughout Telogen.
- Axin2 gene is only expressed in the outer bulge cells, so the cells there retain their stem cell potency, which enables the hair to grow again by entering a new anagen phase.
- Stem cell potency simply means that these cells have the ability to differentiate into different types of cells.
- What are Wnt proteins? They are a family of signalling molecules, involved in regulation and coordination of cell–cell adhesion and gene transcription.
- In the inner bulge cells, the Wnt proteins are inactive, this means that they are already differentiated and can no longer promote hair growth.
- There is a gene that codes for the secretion of Wnt proteins inhibitors (same as there is a gene that codes for the secretion of Wnt proteins, homeostasis must be maintained) and the bulge cells express these bulge inhibitors:
- Dickopf 3 or Dkk3, and
- Secreted frizzled-related protein 1 or SFRP1, our main interest here.
- The hair growth inhibitor Dkk3 stays localised in the inner bulge during the anagen phase.
- The outer bulge cells usually produce their own Wnt signals (autocrine signalling). If Wnt signalling is stopped in these outer bulge cells, they stop being able to contribute to hair growth (as they lose their stem cell potency), and they go through premature differentiation.
- This is key: Wnt proteins signalling in the outer bulge cells maintain hair growth, but SFRP1 would suppress it as it is an inhibitor of Wnt proteins.
- SFPR1 wouldn’t matter as much if it stayed localised in the inner bulge, but it’s the Dkk3 that’s localised there, and those cells are already differentiated, and stay inactive – and that’s because of the Dkk3.
- The cells of the outer bulge are what matter here, in order for the hair to be able to re-enter anagen, once the quiescence phase is over. Otherwise, the telogen phase is increased and the follicle can remain in kenogen (empty) and hair doesn’t grow again because the bulge cells have lost their ability to differentiate and hence build a new hair shaft.
- So, this autocrine signalling in the outer bulge maintains stem cell potency throughout the quiescence and growth stages of the hair cycle. However, paracrine Wnt inhibition of inner bulge cells reinforces differentiation (which is good for the hair to maintain the growth cycle, but bad if the outer bulge cells are also affected, which is what SFRP1 does).
This raises another question: does that then mean that androgens, specifically DHT, have nothing to do with androgenetic hair loss (AGA)? Are there alternative theories for AGA?
This is an excellent question, because despite DHT being held as the unquestionable culprit for AGA, there are a few loopholes in the aetiopathogenesis of AGA, which is mostly based on the androgen-sensitive/insensitive hair follicle concept.
We can explore these alternative theories in a future article.
Jacky van Driel-Nguene.
Cystine Trichology Clinic, Amsterdam
www.cystine.nl IG: @cystinehaircare