Cardiomyopathy of Duchenne muscular dystrophy: pathogenesis and prospect of membrane sealants as a new therapeutic approach.
Duchenne muscular dystrophy (DMD) is a devastating progressive disease of striated muscle deterioration. This fatal X-linked disorder results from the loss of the protein dystrophin, which in turn causes striated muscle membrane instability. Cardiac dysfunction is a growing problem in patients with DMD, but relatively little is known about the pathophysiology of the dystrophic heart. At present, there is no effective treatment for DMD and the current clinical approaches are primarily supportive in nature. This review will discuss the pathogenesis of DMD in the heart and discuss how these pathogenic processes have led to a new class of agents directed specifically at restoring membrane integrity to dystrophic myocardium. The tri-block poloxamers, specifically poloxamer 188 (P188), are able to stabilize the membranes of dystrophic myocardium in animal models and may offer a new therapeutic approach for cardiac disease in DMD.
Townsend
DeWayne
D
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA. dtown@umich.edu
Yasuda
Soichiro
S
Metzger
Joseph
J
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D009202:Cardiomyopathies / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D002462:Cell Membrane / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology; D020442:Poloxamer / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013314:Stress, Mechanical; D013501:Surface-Active Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D013501:Surface-Active Agents; D020442:Poloxamer