The University of Michigan researchers report in the latest issue of Nature a promising new therapeutic way to limit heart damage in patients with Duchenne muscular dystrophy:
The mutation in the dystrophin gene causes the progressive deterioration of skeletal muscles seen in people with MD. But the mutation affects cardiac muscle, too. Many people with Duchenne muscular dystrophy die in their 20s from heart failure caused by cardiomyopathy, a gradual weakening of the heart muscle. Heart failure is the second leading cause of death in DMD.
The chemical sealant that protected hearts in dystrophic mice from damage is called poloxamer 188. According to Joseph M. Metzger, Ph.D., the U-M scientist who directed the research, poloxamer 188 can insert itself into small holes in cell membranes just like “a finger in a dike”.
The U-M study will be published July 17 in Nature as an advance online publication.
The study is important because it is the first to show what happens to heart muscle cells called myocytes in the absence of dystrophin, and the first study to demonstrate a new, promising approach to repair the damage. The study’s authors emphasize, however, that several years of additional animal research will be required before the treatment could be tested in human patients.
“Most people think of the heart as a pump,” explains Metzger, a professor of molecular and integrative physiology and of internal medicine in the U-M Medical School. “They say their heart is failing, because it’s not pumping hard enough. That can be true, but another major problem is poor function during the relaxation phase when the heart fills with incoming blood. In our study, we found that cardiac myocytes in dystrophin-deficient mice don’t relax and lengthen as readily as cardiac myocytes in normal mice. They are stiffer than normal heart muscle cells, and vulnerable to damage when stretched.
“That’s where poloxamer 188 comes in,” Metzger adds. “It assists the heart to be more compliant during the relaxation phase–allowing more blood to flow into the heart. We demonstrated this effect at the level of individual heart muscle cells, and it turned out to be true at the organ level, also.”
More details of this fascinating research…
The BBC coverage…
