%0 Journal Article
%T Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa.
%A Tartaglia G
%A Fuentes I
%A Patel N
%A Varughese A
%A Israel LE
%A Park PH
%A Alexander MH
%A Poojan S
%A Cao Q
%A Solomon B
%A Padron ZM
%A Dyer JA
%A Mellerio JE
%A McGrath JA
%A Palisson F
%A Salas-Alanis J
%A Han L
%A South AP
%J EMBO Mol Med
%V 16
%N 4
%D 2024 Apr 10
%M 38462666
%F 14.26
%R 10.1038/s44321-024-00048-8
%X 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.