What Does Blocking Myostatin Do?

Blocking the protein known as myostatin, which limits muscle growth, has been under intense investigation as a strategy for the muscular dystrophies since 2002, when scientists found that mice with Duchenne muscular dystrophy (DMD) that were bred without myostatin were stronger and more muscular than their counterparts with normal myostatin levels.

In 2005, Wyeth Pharmaceuticals of Collegeville, Pa., launched a clinical trial of a myostatin blocker in three types of MD. The trial is now closed, and the results are under analysis.

MDA-supported researchers have continued studying the effects of myostatin and myostatin blocking in mice.

Myostatin doesn’t affect heart muscle

Mice lacking myostatin don’t develop enlarged hearts, an abnormality that some researchers had feared might occur, reports a group that included MDA grantee Kathryn Wagner at Johns Hopkins University in Baltimore. On the other hand, in mice missing both myostatin and dystrophin, with a disease resembling DMD, a lack of myostatin didn’t prevent the development of scar tissue in the heart, as some researchers had hoped it might.

The researchers, who reported their findings online March 1 in Neuromuscular Disorders, say their data “do not support a cardiac effect in the complete absence of myostatin and therefore would not predict a significant impairment nor improvement in the cardiac function of patients treated with myostatin inhibitors such as are now in clinical trials.”

They add, however, that extending these mouse findings to human patients must be done with extreme caution, because humans treated with myostatin inhibitors will have had myostatin during their development; and because mouse DMD and human DMD are somewhat different.

Muscles can get bigger but weaker

In the Feb. 6 issue of Proceedings of the National Academy of Sciences, MDA grantee Helge Amthor at University Hospital of Essen in Germany, and colleagues, reported that mice bred not to produce any myostatin or to produce an abnormal form of the protein developed muscles that were larger, but weaker, than those of normal mice. None of the mice had muscular dystrophy.

Wagner is relatively unconcerned. She says mice that are closely related and bred to each other, as were the animals in these experiments, often show muscle abnormalities.

“It’s hard to know how to generalize results from a very inbred line of mice that were used in this paper,” she says. “My basic feeling is that I just don’t know how transferable these results are to other mouse populations or to humans.”