Grant: Project Grant

Duchenne muscular dystrophy (DMD) is a fatal disease in which most muscles, including the diaphragm and other breathing muscles, are progressively destroyed and replaced by scar tissue. We plan to evaluate whether interventions that affect the function of macrophages, which are by far the most abundant inflammatory cells in DMD muscles, are effective in treating the disease. This will include testing a new drug called drug cenicriviroc, which blocks receptors that are very important in attracting harmful macrophages during early disease. Other drugs we plan to study, called macrophage stimulating factors, work in an entirely different way which could be useful in favouring beneficial macrophages at the later stages of DMD. We are entering an era of what has been called "personalized" medicine. One practical application of personalized medicine can be summarized as "Giving the right drug to the right patient at the right time". Unfortunately, the current drug management of DMD is based on a "one size fits all" approach. Therefore, in addition to assessing the effectiveness of these drugs, we will also try to identify new blood tests called "biomarkers" that help to predict which drug works best at a given stage of the disease. The majority of outcomes in our studies will be determined in the diaphragm because it is the most severely affected skeletal muscle in our mouse model of DMD with respect to fibrosis and muscle weakness, and it most closely resembles what is found in human patients. We will also do preliminary exploratory studies of our biomarkers by taking blood samples from DMD patients in our clinic. The risk of the medications we are studying is low relative to their potential benefit and especially compared to the major adverse effects associated with the current standard treatment (corticosteroids). All of these drugs could be rapidly moved to the clinic for use in DMD patients if our studies are successful.