Blocking Myostatin Protein Could Treat Muscular Dystrophy

July 11, 2002, Vancouver, Canada — At an international meeting partly sponsored by MDA, two research groups reported that blocking the action of a protein called myostatin might be an effective way to treat Duchenne muscular dystrophy and perhaps other muscle-wasting diseases.

In previous work, scientists found they could create muscle-bound mice by deleting the gene for myostatin — a secreted protein that inhibits muscle growth.

In a new study presented Wednesday at the 10th International Congress on Neuromuscular Diseases in Vancouver, Kathryn Wagner and colleagues at Johns Hopkins University in Baltimore bred those myostatin-negative mice to mice with Duchenne MD. The offspring had significantly larger, stronger muscles than Duchenne mice with intact myostatin genes, and had less evidence of fibrosis – the replacement of muscle by fat and connective tissue.

In a second study, Tejvir Khurana and his group at the University of Pennsylvania in Philadelphia found they could prevent muscle wasting in Duchenne mice by giving them injections of a protein that blocks myostatin function.

The protein is an antibody – one of the Y-shaped missiles that immune cells use to attack bacteria and other foreign substances – specially manufactured to target myostatin.

When young mice with Duchenne were given twice weekly injections of the antibody into the abdominal cavity, their respiratory (breathing) muscles showed reduced signs of degeneration compared to those of untreated mice. The treated mice were also larger and stronger than untreated mice, and had lower blood levels of creatine kinase (CK) — a protein that leaks out of damaged muscle into the bloodstream. (For reasons that aren't clear, in Wagner's study, deleting the myostatin gene didn't lower CK levels in mice with Duchenne.)

Khurana said his study is unique because it moves beyond genetic manipulation. In several studies, researchers have bred corrective genes into mice with Duchenne — including the gene for dystrophin, the protein that's missing in the disease — and effected at least partial protection against muscle wasting. While these experiments have set the stage for gene therapy, as yet there's no effective way to inject genetic material and deliver it throughout the mouse — or human — body, Khurana noted.

Next, Khurana's group plans to test anti-myostatin antibodies in dogs with Duchenne MD — a high benchmark for assessing delivery and effectiveness since the dogs are larger and have a more severe disease than the mice.

Wyeth, a biotechnology company based in Collegeville, Pa., developed the anti-myostatin antibodies used in the current studies by injecting myostatin into myostatin-negative mice and filtering their blood. The company tentatively plans to test the antibodies against age-related muscle wasting and several muscle-wasting diseases, including other forms of muscular dystrophy and diabetes, a Wyeth spokesperson said. But it's likely that human-derived antibodies will be required for clinical use.