Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa

<jats:title>Abstract</jats:title><jats:p>Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFβ pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases.</jats:p>

Tartaglia, G., Fuentes, I., Patel, N., Varughese, A., Israel, L. E., Park, P. H., Alexander, M. H., Poojan, S., Cao, Q., Solomon, B., Padron, Z. M., Dyer, J. A., Mellerio, J. E., McGrath, J. A., Palisson, F., Salas-Alanis, J., Han, L., & South, A. P. (2024). Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa. EMBO Molecular Medicine, 16(4), 870-884. https://doi.org/10.1038/s44321-024-00048-8