CTLA4-Ig disrupts muscle fibrosis in the mdx mouse model of Duchenne muscular dystrophy
Despite advancements in our understanding of the immunobiology of Duchenne muscular dystrophy (DMD), previous findings were not translated into improvements in clinical practice. The standard clinical treatment for DMD includes administration of non-specific anti-inflammatory corticosteroids that provide limited benefits for patients and produce non-target effects that impair muscle regeneration. Thus, the search for an efficacious immunotherapy without adverse effects remains imperative. Because DMD pathology is exacerbated by fibrotic mechanisms mediated by myeloid and fibrogenic cells, we examined the effect of an immune suppressing fusion protein consisting of cytotoxic T-lymphocyte-associated protein4 and immunoglobulin G (CTLA4-Ig) in the mdx murine model of DMD. We found that CTLA4-Ig ameliorates pathology, via the disruption of fibrotic mechanisms, as treatment reduced collagen accumulation and expression in dystrophic muscle. These findings indicate that CTLA4-Ig treatment has inhibitory effects on profibrotic cells that exacerbate DMD pathology and could potentially serve as a promising treatment option for patients with DMD.