Grant: Project Grant

Duchenne muscular dystrophy (DMD), the most common genetic muscle disease, is lethal with no cure at this point in time. Most patients succumb to respiratory failure, which is caused by gradual destruction of the diaphragm, the main breathing muscle. The muscle pathology in DMD is characterized by chronic inflammation with a prominent invasion by immune cells known as macrophages. Previous studies performed by our lab and others demonstrate that reducing certain types of inflammatory macrophages can improve diaphragm muscle function. We believe that modulating inflammation can also improve the local tissue environment in a way that will permit more effective gene therapy for the disease. Therefore, our proposal seeks to identify strategies for therapeutically manipulating macrophage function in the DMD diaphragm using a pre-clinical mouse model of the disease which shares the same genetic defect as human patients. Clinically, these therapies could offer an exciting new avenue for ameliorating respiratory outcomes in patients suffering from DMD as well as other forms of muscular dystrophy.