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

Abstract

Human hair growth can be monitored for several months after the transplantation of scalp samples from men with androgen-dependent alopecia on to female nude mice. Hair production from balding sites has been shown to be inhibited in testosterone-conditioned nude mice. We used this recently reported model to study the effect of a new non-steroidal antiandrogen-RU58841-on human hair growth. Twenty productive scalp grafts from balding men were maintained for 8 months after grafting on to nude mice, and hair production was monitored monthly for 6 months. All mice were conditioned by the topical application of testosterone (testosterone propionate, 300 micrograms in 10 microL; 5 days/week) on the non-grafted flank. The scalp samples were divided equally according to the estimated hair production potential, which was based on the amount of hair present on the scalp samples before grafting. Each of the two equal groups of grafts was further allocated at random to be treated topically (5 days/week) with blinded solutions of either RU58841 1% in ethanol, or ethanol as a control. Twenty-eight active follicles appeared on the 10 control grafts. Among them only two follicles (7%) initiated a second hair cycle. However, the 10 RU58841-treated grafts bore a total of 29 active follicles, and eight of them (28%) showed a second cycle. The values for the linear hair growth rates (LHGR) were significantly (P < 0.04) higher in the RU58841-treated group. Recycling and increased LHGR indicate a positive action for RU58841 on human hair growth from balding samples grafted on to testosterone-conditioned nude mice, and encourage a clinical trial to evaluate its potential in the treatment of androgen-dependent alopecia.

Fluridil, a Rationally Designed Topical Agent for Androgenetic Alopecia: First Clinical Experience

“…7 It is, nevertheless, probable that in humans, topical flutamide induces systemic antiandrogenic effects since at least 16% is transcutaneously resorbed. 8 Preclinical data of another oral antiandrogen, an N-substituted aryl hydantoin, RU-58841 (Figure l), suggested topical safety since the cutaneous resorption was low, 9,10 however, one of the metabolites proved stable and strongly antiandrogenic, 11 and further development was abandoned. Another agent used in AGA is minoxidil, an antihypertensive drug which, by a mechanism yet to be clarified, increases hair thickness and anagen count.…”

Alternative synthesis of the anti-baldness compound RU58841

“…4 Further work by De Brouweri et al conrmed the effect of RU58841 as an antiandrogen and baldness treatment by observing hair re-growth on bald human scalp segments that had been graed to mice. 8 As well as empirical studies, the biochemistry of RU58841 and other hydantoins have been evaluated for their effect as nonsteroidal testosterone inhibitors. 9 As the synthesis of RU58841 by Battmann et al (Fig.…”

Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia

“…A gel formulation of flutamide has been proposed to limit the systemic resorption [Sintov et al, 2000], but no clinical data have been reported. An experimental AA, N-substituted aryl hydantoin RU-58841, proved topically active in rodent and simian AGA models De Brouwer et al, 1997;Matias and Gaillard, 1995;Obana et al, 1997;Pan et al, 1998], but detection of a strongly antiandrogenic metabolite suggested that the compound was systemically resorbed, and further development has apparently been abandoned [Cousty-Berlin et al, 1994].…”