期刊
BRITISH JOURNAL OF DERMATOLOGY
卷 183, 期 1, 页码 114-120出版社
WILEY
DOI: 10.1111/bjd.18718
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- Ram Family Foundation
- German-Israeli Foundation
- Blavatnik Center for Drug Discovery Tel Aviv University - Blavatnik Family Foundation
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 often 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. Objectives As gentamicin has been shown to mediate ribosomal read-through, we aimed to ascertain 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 in vitro the ability of gentamicin to induce translational read through across a causative CDSN mutation. Results Using a reporter assay, we initially showed that gentamicin induces read-through activity across an HSS-causing nonsense mutation. Gentamicin was further shown to rescue corneodesmosin translation in primary keratinocytes obtained from a patient with HSS. To validate the in vitro data, 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. Conclusions Our findings indicate that topical gentamicin should be considered as a potential therapeutic modality in HSS.
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