How Does RU58841 Treat Baldness?
Each hair grows out of a follicle that is embedded in the skin. The hair itself is not alive, but the base of the hair follicle, called the papilla, is composed of very active cells. They divide faster than any other cells in the body, and therefore require a lot of nourishment, provided by a rich bed of tiny blood vessels that surround the papilla. The cells in the papilla produce the complicated structure we call hair. Human scalp hair grows about 15 centimeters per year (1).
Hair growth occurs in cycles. Unlike most mammals that grow hair seasonally, human scalp hair growth cycles are essentially random. Most of the hair follicles at any given time are in the active growth phase, called anagen. Each hair follicle spends 2 to 6 years rapidly growing hair during the anagen phase. At some point, however, each hair follicle enters a phase called catagen that lasts for about 3 weeks. After categen, the hair follicle enters a resting phase called telogen that normally lasts for up to 100 days. During this period of time, the hair produced by the follicle is usually shed. At any given time, around 8% of the hair follicles on the head are in telogen and are shedding hair. Shedding 25 to 100 hairs per day is normal for most people. After resting and shedding the old hair, each hair follicle re-enters anagen and begins to produce a new hair.
In people affected by androgenic alopecia, the presence of male hormones (DHT) causes the hair follicle to spend an excessive amount of time in telogen instead of quickly re-entering anagen. In addition, each time a hair follicle goes through telogen in the presence of DHT the hair follicle shrinks. After a few growth cycles, the shrunken hair follicle is only capable of producing tiny fine hairs called vellum. RU58841 blocks DHT from binding to the receptors in the hair follicles, allowing the hair follicle to re-enter anagen quickly after telogen. Blocking DHT also prevents the hair follicle from shrinking during telogen. In the presence of RU58841, the hair follicles function normally rather than spending excessive amounts of time resting and shrinking.
RU58841 was originally synthesized during experiments intended to discover a potent androgenic (male hormone) blocking agent (2). Many health conditions, everything from acne to prostate cancer, can be treated by blocking male hormones. However, administering androgenic blockers systemically causes a lot of severe side effects. For conditions only affecting the skin, if the blocking agent can be applied to just the skin, it can treat the problem locally without causing side effects.
Clinical studies in monkeys, who are affected by androgenic alopecia just like people, have shown that topical application of RU58841 completely blocks the balding process and also stimulates hair re-growth while baldness progression continued in the control group (see below) (3) .
To ensure that these results apply to people, an additional study using human skin affected by androgenic alpecia was also conducted and found similar results (4). Because the drug is applied to the skin, where it can easily penetrate the base of the hair follicles, it does not enter the systemic circulation. Because it is only acting locally, it has no systemic side effects.
Human volunteers report that application of RU58841 to the scalp completely stops the balding process after 4 to 6 months of regular use. Once the hair follicles have been protected from DHT for an extended period of time, they seem to start to recover and begin to re-grow hair. Most volunteers also use minoxidil to encourage hair re-growth. Minoxidil improves blood circulation to the hair follicle, nourishing the cells as they grow hair. No systemic side effects have ever been reported in association with application of RU58841 to the scalp.
(2) J Steroid Biochem Mol Biol. 1994 Jan;48(1):55-60. RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism.
(3) Endocrine. 1998 Aug;9(1):39-43. Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques.
(4) Br J Dermatol. 1997 Nov;137(5):699-702. A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice.