New Compound Protects Hearts From DMD Damage

Investigators at the University of Michigan in Ann Arbor have found that a synthetic compound known as poloxamer 188 (p188) can protect heart muscle cells in mice lacking the protein dystrophin, which have a muscle disease resembling Duchenne muscular dystrophy (DMD).

Soichiro Yasuda and colleagues, who published their results online July 17 in Nature, found that when they added p188 to heart muscle cells from dystrophin-deficient mice, the cells’ resistance to stress matched that of cells from healthy mice. They believe the drug may shore up the fragile cell membranes seen in DMD.

Next, they gave some of the mice an intravenous infusion of dobutamine, a drug that increases heart rate and blood pressure, and another group an infusion of dobutamine preceded by intravenous p188.

Several of the 10 DMD-affected mice in the first group experienced acute heart failure, which didn’t occur in the mice that received p188.

“If issues of dosing and long-term safety can be addressed, our results indicate that membrane-sealing poloxamers could represent a new class of therapeutic agents” for heart muscle damage associated with DMD and possibly other types of MD involving defects in the muscle-cell membrane, the authors say.

John Quinlan, an MDA grantee at the University of Cincinnati who is studying cardiac problems in DMD-affected mice and is also interested in p188, said, “This work is exciting and cause for hope. The Michigan team has provided us with a better understanding of how DMD attacks cardiac function on a cellular level. Most importantly, they showed how p188 has both beneficial action on reversing cellular damage and improving heart function under stressed conditions.”