Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa

Grace Tartaglia, Ignacia Fuentes, Neil Patel, Abigail Varughese, Lauren E. Israel, Pyung Hun Park, Michael H. Alexander, Shiv Poojan, Qingqing Cao, Brenda Solomon, Zachary M. Padron, Jonathan A. Dyer, Jemima E. Mellerio, John A. McGrath, Francis Palisson, Julio Salas-Alanis, Lin Han, Andrew P. South

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)870-884
Number of pages15
JournalEMBO Molecular Medicine
Issue number4
Publication statusPublished - 2024 Apr 15

All Science Journal Classification (ASJC) codes

  • Molecular Medicine


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