{Reference Type}: Journal Article
{Title}: Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa.
{Author}: Tartaglia G;Fuentes I;Patel N;Varughese A;Israel LE;Park PH;Alexander MH;Poojan S;Cao Q;Solomon B;Padron ZM;Dyer JA;Mellerio JE;McGrath JA;Palisson F;Salas-Alanis J;Han L;South AP;
{Journal}: EMBO Mol Med
{Volume}: 16
{Issue}: 4
{Year}: 2024 Apr 10
{Factor}: 14.26
{DOI}: 10.1038/s44321-024-00048-8
{Abstract}: 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.