Recent studies to establish an effective treatment for Duchenne Muscular Dystrophy (DMD) have discovered that drugs or molecules used to inhibit myostatin - a protein that inhibits muscle growth - might prove to be the anticipated answer.
MDA grantee Kathryn Wagner of John Hopkins University showed in a new study, published online, that muscle mass and strength in mice with DMD is increased by the loss of the myostatin gene. She teamed with Hopkins geneticist Se-Jin Lee to create a strain of mice lacking the myostatin gene which were later bred with mice with DMD. They found that the offspring had significantly larger, stronger muscles than diseased mice with an intact myostatin gene and the offspring also had less fibrosis (the replacement of muscle by fat and connective tissue).
Another similar study was carried out by Tejvir S. Khurana of the University of Pennsylvania who used antimyostatin antibody, developed by scientists from Wyeth Pharmaceuticals of Cambridge, and studied its effect on mice with DMD. He injected the antibody into the abdominal cavity of mice with DMD before they showed signs of the disease. After three months, he found that the mice injected with the antibody had increased muscle mass and strength in their leg muscles, and less degeneration and fibrosis of their respiratory muscles, when compared to untreated mice. They also had lower blood levels of creatine kinase (CK) a protein that leaks out of damaged muscle.
While Kathryn believes that there is a real possibility for moving forward in clinical trials with myostatin inhibition, Khurana is more cautious, noting that the myostatin-blocking antibodies he used were made in mouse cells to target mouse myostatin and that it is necessary to make specific human antibodies before proceeding to clinical trials. However, Kathryn indicated that there are other ways of inhibiting myostatin and that antibodies are farthest in the pipeline.
Khurana cautioned that there is a real risk in inhibiting myostatin in an unregulated and unmonitored fashion, as this could deplete the cells at an accelerated pace and actually worsen the muscular dystrophy. He also added that long-term inhibition of myostatin might not be safe for youngsters with DMD, since the protein regulates muscle progenitor cells (immature cells that form muscle). He is now addressing these issues in further studies of mice and is also planning to test myostatin blockade in dogs with DMD, since dogs are larger and have a more severe disease than the mice. He added that testing the strategy in animal models of limb-girdle muscular dystrophy is also in the pipeline.
Kathryn Wagner, on the other hand plans to take these studies further by "switching off" the myostatin gene in mice with DMD at different time points to determine if the treatment is still effective at late stages of the disease.