Using cell-specific AR knockout mice, the team went on to show that it is AR on infiltrating macrophages, rather than on resident keratinocytes or dermal fibroblasts, that plays a critical role in delaying wound healing and collagen deposition but that AR on keratinocytes and fibroblasts plays an opposing role in the regulation of re-epithelialization. Examination of inflammatory mediators showed that increased local TNF-α production following AR activation on macrophages plays a critical role in suppressing wound healing.
Topical application of ASC-J9, an anti-AR compound that causes increased AR degradation and reduced AR transactivation, was shown to accelerate wound healing. Earlier in vitro and in vivo studies have shown that ASC-J9 reduces AR-promoted tumour growth in liver and bladder cancer as well as AR-mediated spinal and bulbar muscular atrophy, with little influence on serum testosterone concentrations. The present study, which is published in the Journal of Clinical Investigation, suggests that topical treatment with ASC-J9 also has the potential to be effective in promoting wound healing.
ASC-19 is currently undergoing clinical trials for the treatment of acne and alopecia.