Browsing by Author "Varughese, Abigail"
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Publication Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa(2024) Tartaglia, Grace; Fuentes, María; Pate,Neil; Varughese, Abigail; Pyung, Lauren; Pyung, Israel; Alexander, Michael; Poojan, Shiv; Cao, Qingqing; Solomon, Brenda; Padron, Zachary; Dyer, Jonathan; Mellerio, Jemima; McGrath, John; Palisson, Francis; Salas, Julio; Han, Lin; South, AndrewRecessive 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.