Male androgenetic alopecia (MAA) is the most common form of hair loss in men, affecting 30-50% of men by age 50. It occurs in a highly reproducible pattern, preferentially affecting the temples, vertex and mid frontal scalp.
Although MAA is often regarded as a relatively minor dermatological condition, hair loss impacts self-image and is a great cause of anxiety and depression in some men.
Currently only two FDA-approved hair growth promoters, minoxidil and finasteride, are available for treatment of MAA. However, both drugs have moderate side effects and often produce disappointing hair regrowth results.
Dr. Nathan Hawkshaw from the Centre for Dermatology Research at the University of Manchester and co-authors sought to develop new ways to promote human hair growth with the hope of finding novel, well-tolerated agents for treating MAA.
The approach was to first identify the molecular mechanisms of an old immunosuppressive drug, Cyclosporine A (CsA).
CsA has been commonly used since the 1980s as a crucial drug that suppresses transplant rejection and autoimmune diseases. However, it often has severe side-effects, the least serious of which is that it enhances cosmetically unwanted hair growth.
The researchers carried out a full gene expression analysis of isolated human scalp hair follicles treated with CsA. This revealed that CsA reduces the expression of the secreted frizzled related protein 1 (SFRP1), a protein that inhibits the development and growth of many tissues, including hair follicles.
This identifies a completely novel mechanism of action of this old and widely used immunosuppressant.
“Our study also explains why CsA so often induces undesired hair growth in patients as it removes an inbuilt and potent molecular brake on human hair growth,” the scientists said.
“The inhibitory mechanism is completely unrelated to CsA’s immunosuppressive activities, making SFRP1 a new and highly promising therapeutic target for anti-hair loss strategies.”
After some detective work, the team found that a compound called WAY-316606 targets the same mechanism as CsA by specifically antagonizing SFRP1.
When they then treated hair follicles with WAY-316606, the unrelated agent also effectively enhanced human hair growth like CsA.
“The external application of WAY-316606 or similar compounds to balding human scalp may promote hair growth to the same magnitude as CsA or even better, but without its side effects,” Dr. Hawkshaw said.
“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.”
“This makes our research clinically very relevant, as many hair research studies only use cell culture.”
N.J. Hawkshaw et al. 2018. Identifying novel strategies for treating human hair loss disorders: Cyclosporine A suppresses the Wnt inhibitor, SFRP1, in the dermal papilla of human scalp hair follicles. PLoS Biol 16 (5): e2003705; doi: 10.1371/journal.pbio.2003705