Treatment of hereditary hypotrichosis simplex of the scalp with topical gentamicin

BACKGROUND: Hypotrichosis simplex of the scalp (HSS) is characterized by progressive loss of scalp hair that results in almost complete baldness at a young age. HSS is caused by dominant nonsense mutations in CDSN encoding corneodesmosin, leading to the formation of an amyloid-like material which interferes with normal hair follicle cycle.

OBJECTIVE: Since gentamicin has been shown to mediate ribosomal read-through across nonsense mutations, we aimed at ascertaining its therapeutic efficacy in a small series of patients carrying a recurrent mutation in CDSN.

METHODS: We used a green fluorescence reporter assay system, confocal microscopy and Western blot analysis to ascertain the ability of gentamicin to induce translational read-through across a causative CDSN mutation. We then conducted an open-label pilot trial in 4 HSS patients carrying a nonsense mutation in CDSN. Patients applied topical gentamicin 0.1% on their scalp for 6 months. Hair growth was determined by patients’ global photographic response and SALT (Severity of Alopecia Tool) Score.

RESULTS: Gentamicin was shown in vitro, using a reporter assay as well as patient cells, to restore full-length corneodesmosin expression. Topical gentamicin treatment resulted in a significant improvement in patient`s hair growth and reduction in SALT score after 6 months of treatment.

CONCLUSIONs: Our findings indicate that topical gentamicin should be considered as a potential therapeutic modality in HSS.