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Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa

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dc.contributor.authorTartaglia, Grace
dc.contributor.authorFuentes, María
dc.contributor.authorPate,Neil
dc.contributor.authorVarughese, Abigail
dc.contributor.authorPyung, Lauren
dc.contributor.authorPyung, Israel
dc.contributor.authorAlexander, Michael
dc.contributor.authorPoojan, Shiv
dc.contributor.authorCao, Qingqing
dc.contributor.authorSolomon, Brenda
dc.contributor.authorPadron, Zachary
dc.contributor.authorDyer, Jonathan
dc.contributor.authorMellerio, Jemima
dc.contributor.authorMcGrath, John
dc.contributor.authorPalisson, Francis
dc.contributor.authorSalas, Julio
dc.contributor.authorHan, Lin
dc.contributor.authorSouth, Andrew
dc.date.accessioned2025-01-16T16:19:01Z
dc.date.available2025-01-16T16:19:01Z
dc.date.issued2024
dc.description.abstractRecessive 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.
dc.description.versionVersión Publicada
dc.identifier.citationTartaglia 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. Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa. EMBO Mol Med. 2024 Apr;16(4):870-884. doi: 10.1038/s44321-024-00048-8
dc.identifier.doihttps://doi.org/10.1038/s44321-024-00048-8
dc.identifier.urihttps://hdl.handle.net/11447/9663
dc.language.isoen
dc.subjectAntivirals
dc.subjectCollagen
dc.subjectDrug Repurposing
dc.subjectFibrosis
dc.subjectRecessive Dystrophic Epidermolysis
dc.titleAntiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceEMBO molecular medicine
dspace.entity.typePublication

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