Protein holds promise for new gene therapy strategy for muscle-wasting diseases

Scientists at the Research Institute at Nationwide Childrens Hospital have found the role of a protein that holds promise for new clinical treatments to combat musculoskeletal diseases, including Duchenne muscular dystrophy (DMD).

Washington, Mar 11 : Scientists at the Research Institute at Nationwide Children's Hospital have found the role of a protein that holds promise for new clinical treatments to combat musculoskeletal diseases, including Duchenne muscular dystrophy (DMD).

Led by Brian Kaspar, PhD, a principal investigator in the Center for Gene Therapy at The Research Institute and an assistant professor of Paediatrics at The Ohio State University, the study focused on a protein called follistatin (FS).

In the study, researchers used a single injection, gene-delivery strategy involving FS, to treat the hind leg muscles of mice.

They found increased muscle size and strength, quadruple that of mice treated with proteins other than FS. The muscle enhancements were shown to be well-tolerated for more than two years.

Dr. Kaspar said that increased muscle mass and strength were also evident when this strategy was tested using a model of DMD.

Apart from the injected hind leg muscles, strengthening effects were also shown in the triceps. Also, fibrosis, abnormal formation of scar tissue and a hallmark of muscular dystrophy, was decreased in FS-treated animals.

"We believe this new FS strategy may be more powerful than other strategies due to its additional effects, including its ability to reduce inflammation," Dr. Kaspar said.

The researchers found that the strategy had no negative effects on the heart or reproductive ability of either males or females.

The results were also replicated in older animals, suggesting that this strategy could be useful in developing clinical treatments for older DMD patients.

"This research provides evidence of multiple potential treatment applications for muscle diseases including, but not limited to, muscular dystrophy," said Jerry Mendell, MD, director of the Center for Gene Therapy at The Research Institute, a co-author on the study, and professor of Pediatrics in Neurology and Pathology at The Ohio State University.

"These results offer promise for treatment of potentially any muscle-wasting disease, including muscle weakness due to other illnesses, aging, and inflammatory diseases such as polymyositis. Our next step is to pursue clinical trials," Mendell added.

The study is published in the March 11, 2008 issue of the Proceedings of the National Academy of Sciences.

ANI