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.

A Guide to Studying Human Hair Follicle Cycling In Vivo

“…in the context of androgenetic alopecia, also need to consider the intricate hormone-sensitivity of human HFs ( Paus et al , 2014 ) and their keratin expression patterns ( Ramot and Paus, 2014 ); therefore, imitating donor-like hormone levels in host mice (e.g. testosterone) is important ( De Brouwer et al , 1997 ; Krajcik et al , 2003 ; Sintov et al , 2000 ; Van Neste et al , 1991 ).…”

“…HF xenotransplantation is currently the only preclinical assay that permits complete human HF cycling and supports long-lasting human anagen studies in vivo and is therefore a uniquely instructive and indispensable human hair research tool. However, despite several early reports ( De Brouwer et al ., 1997 ; Gilhar et al ., 1988 ; Gilhar et al ., 1998 ; Hashimoto et al ., 2000 , 2001 ; Jahoda et al ., 1996 ; Krajcik et al ., 2003 ; Lyle et al ., 1999 ; Tang et al ., 2002 ; Van Neste et al ., 1989 ), and more recent uses for the experimental induction of alopecia areata ( Gilhar et al ., 2013 ), post-grafting human scalp hair cycle dynamics remain poorly characterized, hindering broader adaptation of this model. Furthermore, as xenografting is inevitably associated with surgery-, wound healing-, reinnervation-, and reperfusion-related phenomena that are absent during normal scalp HF cycling in vivo (see below), a detailed morphological comparison between xenografted and freshly biopsied human scalp HFs is needed.…”

Formulation and evaluation of ciprofloxacin as a topical gel

“…The dialysis cell was inverted and immersed up to 0. 5 cm in 500 ml of phosphate buffer pH7.4 contained in the flask of the dissolution apparatus (collecting medium) [18] . The flask was partially immersed in a large water bath at a constant temperature of 37 °C inside the dissolution apparatus.…”

“…The flask was partially immersed in a large water bath at a constant temperature of 37 °C inside the dissolution apparatus. The stirrer was immersed in the collecting medium and the stirring rate was maintained at 100 r. p. m. [18] . The net release of ciprofloxacin HCl was followed by monitoring the receiver medium concentration for 6 hours, Five milliliters samples where withdrawn with a pipette fitted with a filter from the collecting medium after 0.…”

Discovery of (2S)-N-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-3-(6-(4-cyanophenyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-hydroxy-2-methylpropanamide as a Highly Potent and Selective Topical Androgen Receptor Antagonist for Androgenetic Alopecia Treatment

“…Thus, the urgent need for topical AR antagonists has prompted research in this area. Although there have been reports on topical AR antagonists such as RU-58841 ( 5 ), − fluridil ( 6 ), clascoterone ( 7 ), pyrilut­amide, and GT20029, none has been approved by the FDA. RU-58841 and fluridil were approved for topical treatment of AGA in Indonesia and the Czech Republic, respectively, but have not been widely used due to safety concerns.…”