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

摘要: Duchenne muscular dystrophy (DMD) has as standard pharmacological therapy with corticoisteroids (CS) that decrease inflammation and immune responses present in patients animal models. CS have however limited efficacy important numerous side effects. Therefore, there is a need for new anti-inflammatory pro-tolerogenic treatments could replace or doses of CS. We first assessed the status system dystrophin-deficient rats (Dmdmdx) closely reproduce phenotype DMD patients. Dmdmdx showed increased leukocyte infiltration skeletal cardiac muscles, containing mostly macrophages but also T cells, expression several cytokines. Anti-CD45RC Monoclonal antibody (Mab) treatment induced tolerance models organ transplantation GVHD (Graft Versus Host Disease). observed muscles blood contained CD4+ CD8+ expressing high levels CD45RChigh cells. Treatment young anti-CD45RC MAb corrected muscle strength associated to depletion effectors cells no obvious side-effects. Prednisolone similarly was resulted severe weight loss. Overall, display inflammatory response thus represent useful model analyze tolerogenic DMD. As an example, antibodies improved prednisolone did without complement other therapies