Logo image
Back
Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa
Journal article   Open access   Peer reviewed

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, …
EMBO molecular medicine, v 16(4), pp 870-884
15 Apr 2024
DOI: https://doi.org/10.1038/s44321-024-00048-8
PMID: 38462666
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/s44321-024-00048-8View
Published, Version of Record (VoR) Open

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. The antiviral daclatasvir was identified as an anti-fibrotic compound in a high throughput screen using a novel in vitro model of fibrosis. Daclatasvir improved life quality and survival in a mouse model of recessive dystrophic epidermolysis bullosa (RDEB). Endogenously-produced matrix from primary patient fibroblasts can be utilized as a detachment assay to screen compounds for anti-fibrotic repurposing.Antivirals are a novel class of fibrosis preventatives in RDEB as verified from two library screens.Daclatasvir was our repurposed hit of interest for preventing fibrosis in RDEB.Daclatasvir downregulated the TGFβ signaling pathway targets.Daclatasvir improved the life quality of RDEB mice. The antiviral daclatasvir was identified as an anti-fibrotic compound in a high throughput screen using a novel in vitro model of fibrosis. Daclatasvir improved life quality and survival in a mouse model of recessive dystrophic epidermolysis bullosa (RDEB).

Metrics

1 Record Views
3 citations in Web of Science

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

Source: SDGs in the Output

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Medicine, Research & Experimental
Logo image