Project 2, lead by Dr. Elizabeth McNally at Northwestern University’s Feinberg School of Medicine is designed to 1) to identify and assess modifiers of muscular dystrophy and 2) to understand better the integration between cardiac and pulmonary dysfunction in muscular dystrophy. In the last funding period, we proposed to map modifiers of cardiopulmonary dysfunction using a mouse model of muscular dystrophy. Studies were conducted in the Sgcg mouse model, because this model mirrors what occurs in sarcoglycanrelated limb girdle muscular dystrophies and in Duchenne Muscular Dystrophy. Specifically, cardiac dysfunction is more evident in this model, compared with what is typically seen in the mdx mouse model. Furthermore, it is expected that modifiers mapped using the Sgcg mouse model will translate to other forms of muscular dystrophy because of the overlapping pathogenic mechanisms that underlie many forms of muscular dystrophy. Mutations in dystrophin or the sarcoglycan genes lead to sarcolemma instability. The repetitive disruption of the sarcolemma, as occurs in many forms of muscular dystrophy, triggers a cascade of intracellular and extracellular effects. In skeletal muscle, these events are often associated with inflammation, which accelerates the disease course. In cardiac muscle, the contribution of inflammation is less studied. Recent data suggests that long-term treatment with glucocorticoids has benefit for cardiac function in DMD. Newer data supports the use of mineralocorticoid receptor antagonists to improve cardiac and potentially respiratory function.
|Effective start/end date||8/1/18 → 7/31/19|
- University of Florida (UFDSP00012258//U54AR052646)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (UFDSP00012258//U54AR052646)