Trial could lead to new treatment for most common form of muscular dystrophy

Patients with the most common form of muscular dystrophy, Duchenne, often lose the ability to walk by the time they reach age 12 and typically only live to reach their 20s. Now, University of Florida Health researchers are participating in a key late-stage clinical trial that could lead to a new therapy for some children with this condition.

Sarepta Therapeutics will provide up to $1.6 million to UF Health to serve as a major site for the third phase of a clinical trial that, if successful, could help some patients with Duchenne maintain mobility and pulmonary function longer.

Barry Byrne, M.D., Ph.D.Early results from the first two phases of the clinical trial for a drug called eteplirsen have been promising in some patients with the disease, extending the length of time they were able to walk compared with a control group of study participants who did not receive the drug, said Barry Byrne, M.D., Ph.D., principal investigator for the hub site at UF Health and a professor of pediatrics in the College of Medicine.

Results announced in January from the second phase of the study showed that participants were still able to walk and had stable respiratory function 168 weeks into the study.

Duchenne muscular dystrophy is an inherited condition that occurs when a faulty gene located on a person’s X chromosome prevents the body from producing the protein dystrophin. Dystrophin plays a key role in helping muscles remain intact and protecting them from injury. Because the gene is found on the X chromosome, the condition only affects boys because they have only one X chromosome. Girls have two, giving them an extra dystrophin gene that works properly. 

The hope is that in some Duchenne patients, eteplirsen can be used to produce a shorter-than-typical version of the dystrophin gene. The idea is similar to what occurs naturally in patients with another form of muscular dystrophy, Becker muscular dystrophy, Byrne said.

“The strategy is borrowed from the observation that patients with Becker muscular dystrophy have a truncated protein,” said Byrne, who also serves as director of UF’s Powell Gene Therapy Center. “Dystrophin is the largest protein in the body. Regions of it are repeated. These long, repeated segments of the protein can be shortened and still maintain function.”

Although the method would not be a cure, it could potentially delay the loss of function in Duchenne patients. Patients with Becker muscular dystrophy typically do not decline as rapidly as those with Duchenne. In addition, they have a longer lifespan, often living to middle age and beyond, according to the Muscular Dystrophy Association. 

 “Eteplirsen is designed to edit the incorrect instructions for dystrophin production and lead to a shortened but functional protein,” said Peter Kang, M.D., chief of the division of pediatric neurology and a co-investigator of the study.

About 15 percent of patients with Duchenne would be candidates for this treatment if it is successful in the current clinical trial and approved by the FDA. People whose dystrophin genes contain long segments with errors are not candidates for this approach, Byrne says.           

During the phase III trial, researchers will monitor the effectiveness of the treatment and whether it has any side effects. They will also compare it with other existing treatments. This phase of the study will determine whether the drug will receive approval from the Food and Drug Administration.

In addition to serving as a site where people with Duchenne can receive the drug, the UF Health team will coordinate study efforts at other hospitals across the Southeast.

“We have been very pleased to work with the University of Florida and to select them as one of our 14 hub sites in the country. The clinical trial experience of the site, which includes not only clinical trials but also research in novel cardiac care for boys with DMD, made them an ideal clinical site,” said Edward Kaye, M.D., chief medical officer of Sarepta Therapeutics.

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April Frawley Lacey

Editor / College of Medicine Science Writer

Editor of The Post and a medical writer in the HSC Office of News & Communications. Before joining the HSC News & Communications staff, she was a reporter and assistant...Read More