Immunological characterization of a rat model of Duchenne’s disease and demonstration of improved muscle strength after anti-CD45RC antibody treatment

Duchenne muscular dystrophy (DMD) has as standard pharmacological therapy with corticoisteroids (CS) that decrease inflammation and immune responses present in patients and animal models. CS have however limited efficacy and important and numerous side effects. Therefore, there is a need for new anti-inflammatory and pro-tolerogenic treatments that could replace or decrease doses of CS. We first assessed the status of immune system of dystrophin-deficient rats ( Dmd mdx ) that closely reproduce the phenotype of DMD patients. Dmd mdx rats showed increased leukocyte infiltration in skeletal and cardiac muscles, containing mostly macrophages but also T cells, and increased expression of several cytokines. Anti-CD45RC Monoclonal antibody (Mab) treatment induced immune tolerance in models of organ transplantation and GVHD (Graft Versus Host Disease). We observed that muscles and blood of DMD patients contained T CD4 + and CD8 + expressing high levels of CD45RC high cells. Treatment of young Dmd mdx rats with anti-CD45RC MAb corrected skeletal muscle strength associated to a depletion of effectors CD45RC high T cells with no obvious side-effects. Prednisolone treatment of Dmd mdx rats similarly increased skeletal muscle strength and was also associated to a depletion of effectors CD45RC high cells but resulted in severe weight loss. Overall, Dmd mdx rats display important immune inflammatory response and thus represent a useful model to analyze new anti-inflammatory and tolerogenic treatments for DMD. As an example, a new treatment with anti-CD45RC antibodies improved muscle strength in Dmd mdx rats as prednisolone did but without side effects. Anti-CD45RC therapy could complement other therapies in DMD patients.