Hypotrichosis simplex of the scalp (HSS) is characterized by progressive loss of scalp hair at a young age with often devastating psychological implications for affected children. HSS is often caused by dominant nonsense variants in CDSN encoding corneodesmosin. The resulting mutant protein leads to the formation of an amyloid like material, which interferes with normal hair follicle cycle. Decreasing the level of the mutant protein is therefore expected to result in a clinically beneficial effect. We developed a green fluorescence reporter assay allowing semi-quantification of read-through activity across nonsense mutation in CDSN. Using this system, we observed that gentamicin restores full-length corneodesmosin biosynthesis in a dose-dependent fashion. Gentamicin was further shown to rescue corneodesmosin translation in primary keratinocytes obtained from a patient with HSS. Finally, we conducted a pilot clinical trial where the scalp of four patients was treated topically with gentamicin for 6 months, demonstrating significant improvement as ascertained by the Severity of Alopecia Tool score. Our findings indicate that topical gentamicin should be considered as a potential therapeutic modality in HSS.

ESDR078 - Treatment of hereditary hypotrichosis simplex of the scalp with topical gentamicin

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING