According to researchers from The University of Manchester’s Centre for Dermatology Research, a new drug — originally designed to treat osteoporosis — could help men and women suffering from baldness.
Baldness
The research, which has been published in the journal PLOS Biology, was led by Dr Nathan Hawkshaw and involved the treatment of organ-cultured human scalp hair follicles (HFs) with the immunosuppressive calcineurin inhibitor, Cyclosporine A (CsA) — known to cause excessive hair growth.
Currently, there are only two drugs, approved by the US Food and Drug Administration (FDA), available for the treatment of hair loss — minoxidil and finasteride. Both of these agents, however, only offer moderate side effects and are not universally effective. Other than these pharmacological options, patients are limited to hair transplantation surgery.
In their research, Hawkshaw and colleagues (in the lab of Professor Ralf Paus) looked at novel ways of promoting human hair growth with the aim of finding agents that are well-tolerated for the treatment of androgenetic alopecia.
First-of-all, the team identified the molecular mechanisms of CsA, a commonly used drug since the 80s for the suppression of transplant rejection and autoimmune diseases, which has the side effect of enhancing cosmetically unwanted hair growth.
After performing full gene expression analysis of isolated scalp HFs treated with CsA, it was found that the immunosuppressive agent reduced the expression of a protein that inhibits the development and growth of many tissues, including HFs, SFRP1.
This novel mechanism of action not only explains why CsA often causes undesired hair growth in patients but also makes it a promising therapeutic target for anti-hair loss strategies.
After some work into how and to what extent SFRP1 is inhibited by CsA and the effect that Wnt ligand activity (canonical WNT signalling is inhibited by SFRP1) has on anagen and hair shaft formation, the team revealed that WAY-316606 (an osteoporosis treatment) antagonises SFRP1. This target, which is the same mechanism as that of CsA, meant that when HFs were treated with WAY-316606 hair growth was enhanced.
Therefore, external application of this agent to a balding scalp may promote hair growth to the same degree as CsA except without the severe side effects.
“Thanks to our collaboration with a local hair transplant surgeon, Dr Asim Shahmalak, we were able to conduct our experiments with scalp hair follicles that had generously been donated by over 40 patients and were then tested in organ cultures,” said Dr Hawkshaw. “This makes our research clinically very relevant, as many hair research studies only use cell culture.
“When the hair growth-promoting effects of CsA were previously studied in mice, a very different molecular mechanism of action was suggested; had we relied on these mouse research concepts, we would have been barking up the wrong tree.
“The fact this new agent, which had never even been considered in a hair loss context, promotes human hair growth is exciting because of its translational potential: it could one day make a real difference to people who suffer from hair loss.
“Clearly though, a clinical trial is required next to tell us whether this drug or similar compounds are both effective and safe in hair loss patients.”