Poloxamer 188: Potential Drug Against Muscular Dystrophy

Filed in archive Drugs, Vaccines and Therapeutics on July 18, 2005

In patients with Duchenne muscular dystrophy (DMD), the mutation in the gene responsible for the production of the dystrophin protein cause the progressive deterioration of skeletal, as well as cardiac muscles. In fact, many patients afflicted with the disease die as early as their 20's as a result of cardiomyopathy, a gradual, progressive weakening of the heart muscle.

In the advanced online publication of Nature yesterday, Joseph Metzger of the University of Michigan in Ann Arbor, and his colleagues showed the mechanism how the lack in dystrophin cause the heart muscles to weaken, and suggest a possible drug to combat the disease. Apparently, without dystrophin, heart muscles lose their flexibility and become damaged during the stretching and relaxing it undergoes in order to pump blood. Poloxamer 188 (P188) acts a chemical sealant targeted to repair damages on myocyte membranes cause by the tension during the stretching of the heart muscles.

Using fluorescent dyes and a device developed by Soichiro Yasuda to allow the simultaneous measurement of force and intracellular calcium concentration in individual myocytes, they were able to show that in damaged mice cardiac cells treated with poloxamer 188, cell death was averted. "The chemical acts like a 'finger in a dike', Metzger's team reports, by preventing calcium influx.

"If issues of dosing and long-term safety can be resolved, our research suggests that poloxamer 188 could be a new therapeutic agent for preventing or limiting progressive damage to the hearts of patients," Metzger says. He and his team also want to test the drug on mice with other types of muscular dystrophy. The Duchenne form is just one of nine different versions that affect humans.

Read the Nature news article here.