UCLA

Although there is no cure for Duchenne muscular dystrophy (DMD), patients are commonly prescribed corticosteroids, typically prednisone, to slow disease progression and dampen the immune response. Prednisone promotes transcription of anti-inflammatory genes and reduces transcription of pro-inflammatory genes, leading to downregulation of prostaglandins that recruit immune cells. Because the immune system modulates the severity of pathology in DMD and in mdx mice (a genetic model for DMD), immunotherapy may also be beneficial. Cytotoxic T- lymphocyte-associated protein-4 (CTLA-4) is a negative regulator of the immune system that inhibits activation of cytotoxic T-cells. CTLA4-Ig is a fusion protein that blocks the activation and invasion of macrophages and cytotoxic T-cells in other inflammatory and autoimmune diseases, which suggests that it may also positively affect the pathology of muscular dystrophy. Our lab previously demonstrated that CTLA4-Ig treatment alone is effective in reducing many aspects of mdx pathology. The objective of this study is to determine if the beneficial effects of utilizing CTLA4-Ig are affected by co-administration with prednisone in an mdx mouse model. At the peak of muscular pathology, we found that the combined treatment of prednisone and CTLA4-Ig reduced inflammation, necrosis, and fibrosis in 4-week mdx quadriceps. Because of these promising outcomes, the combination of immunotherapy and corticosteroids may serve as a potential treatment for patients with DMD.