Myxomavirus Serp-1 Protein Ameliorates Inflammation in a Mouse Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is an X-linked disease afflicting 1 in 3500 males that is characterized by muscle weakness and wasting during early childhood, and loss of ambulation and death by early adulthood. Chronic inflammation due to myofiber instability leads to fibrosis, which is a primary cause...

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Bibliographic Details
Published in:Biomedicines 2022-05, Vol.10 (5), p.1154
Main Authors: Andre, Alexander B, Zhang, Liqiang, Nix, Jalen D, Elmadbouly, Nora, Lucas, Alexandra R, Wilson-Rawls, Jeanne, Rawls, Alan
Format: Article
Language:English
Subjects:
Animal models
Cardiomyopathy
Children
Corticosteroids
Cytokines
Diaphragm
Duchenne muscular dystrophy
Duchenne's muscular dystrophy
Fibroblasts
Fibrosis
Immunomodulation
Immunosuppressive agents
Inflammation
Injuries
Laboratory animals
Lymphocytes T
Macrophages
Muscular dystrophy
Musculoskeletal system
Myxoma
Myxoma virus
Pathology
Proteins
serpin
Steroids
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Summary:Duchenne muscular dystrophy is an X-linked disease afflicting 1 in 3500 males that is characterized by muscle weakness and wasting during early childhood, and loss of ambulation and death by early adulthood. Chronic inflammation due to myofiber instability leads to fibrosis, which is a primary cause of loss of ambulation and cardiorespiratory insufficiency. Current standard of care focuses on reducing inflammation with corticosteroids, which have serious adverse effects. It is imperative to identify alternate immunosuppressants as treatments to reduce fibrosis and mortality. Serp-1, a Myxoma virus-derived 55 kDa secreted glycoprotein, has proven efficacy in a range of animal models of acute inflammation, and its safety and efficacy has been shown in a clinical trial. In this initial study, we examined whether pegylated Serp-1 (PEGSerp-1) treatment would ameliorate chronic inflammation in a mouse model for Duchenne muscular dystrophy. Our data revealed a significant reduction in diaphragm fibrosis and increased myofiber diameter, and significantly decreased pro-inflammatory M1 macrophage infiltration. The M2a macrophage and overall T cell populations showed no change. These data demonstrate that treatment with this new class of poxvirus-derived immune-modulating serpin has potential as a therapeutic approach designed to ameliorate DMD pathology and facilitate muscle regeneration.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10051154