P45 THE NOVEL DRUG CS-891 INHIBITS 5"-REDUCTASE ACTIVITY IN THE DERMAL PAPILLA OF HUMAN HAIR FOLLICLES

¹Niiyama S., ²Kojima K., ²Hamada T., ¹Happle R., ¹Hoffmann R. ¹Dept. of Dermatology, Philipp University, Marburg, Germany; ²Sankyo Co Ltd., Tokyo, Japan.

The local conversion of testosterone (T) to the more potent androgen dihydrotestosterone (DHT) by 5“-reductase (5aR) is implicated in the pathogenesis of androgenetic alopecia (AGA). Recently, the effectiveness of finasteride, a selective type 5aR inhibitor, to treat AGA has been documented and previous studies have shown that circulating DHT is lowered by 60-70% in men taking finasteride. The source of the residual circulating DHT is presumed to be due to type 5aR activity which is not affected by finasteride. Several novel compounds with potent dual inhibitory activity on both isoenzymes have been described and CS-891 is one of them. This compound may be similarly effective in the prevention or treatment of AGA. As a prerequisite for such an action CS-891 should be able to inhibit 5aR activity in its target tissue: the hair follicle (HF). Scalp biopsies from healthy volunteers were taken and dermal papillae (DP) were dissected from each biopsy. Groups of six DP were incubated in the presence of ³H-T and CS-891 (at 10 nM, 2 nM, 0.4 nM, 0.1 nM or 0.01 nM) or without treatment for up to 39 hours. Thereafter, HPLC analysis of culture supernatants was performed to detect T-metabolites. Our results show that CS-891 is able to block 5aR activity in isolated DP of human HF in a very effective way. Even doses of 0.01 nM CS-891 inhibited 5aR activity in DP by 59%. Provided the safety profile of CS-891 is proven acceptable, this drug could be effectively used in the treatment of AGA.