New Myostatin Blocker Makes Mouse Muscles 60 Percent Larger

A new compound that blocks myostatin, a natural inhibitor of muscle growth, has increased muscle mass in mice by up to 60 percent in two weeks, a team of scientists announced in the Dec. 13 issue of Proceedings of the National Academy of Sciences (PNAS). The tested mice did not have muscular dystrophy.

Se-Jin Lee at Johns Hopkins University in Baltimore and colleagues from several academic institutions and biotechnology companies, say the new compound blocks myostatin using a different mechanism from a previously developed agent, which is now being tested in clinical trials in patients with certain adult forms of muscular dystrophy. (See “Clinical Trials and Studies” on the MDA Web site for details.)

The original compound, MYO-029, was developed by Wyeth Pharmaceuticals, and is based on an antibody (immune-system protein) that sticks to and interferes with myostatin.

The new compound, ACVR2B, is not an antibody. Instead, it blocks myostatin by providing it with a portion of a molecule that it normally sticks to but not the entire molecule. This partial molecule keeps myostatin from interacting with its normal molecular binding partner; and, without this interaction, myostatin can’t send its usual growth-inhibiting signals to muscle cells.

Lee, a professor of molecular biology and genetics at the Johns Hopkins Institute for Basic Biomedical Sciences, has MDA funding for closely related work on myostatin mechanisms. He says the new inhibitor is very potent, leads to dramatic effects in the mice, and that the effects were “larger and faster than we’ve seen with any other agent and even larger than we expected.”

He cautions, however, that the effects of ACVR2B can be attributed to its ability to block more than just myostatin signaling, and that this is both a benefit and a risk.

“The fact that this new inhibitor can block other [chemicals] in addition to myostatin is a potential down side of using this as a therapeutic, as the potential for side effects could be greater,” he says.

Lee also notes that increasing muscle mass alone isn’t necessarily the answer in muscular dystrophy.

“In general, I am quite optimistic that targeting this pathway will turn out to be an effective way to increase muscle growth,” he says. “But much more work will be required to determine whether this will be a viable approach.”