Duchenne Muscular Dystrophy: New Gene Therapies Increase Production of Vital Protein

Muscular dystrophy, a genetic disease in which muscle fibers are susceptible to damage, can wreak havoc on the body, causing muscles to progressively become weaker and the patient usually requiring a wheel chair.

Statistics show that with many different types of muscular dystrophy, symptoms of the most common variety begin in childhood, primarily in boys. Other types of muscular dystrophy don't resurface again until adulthood, with symptoms ranging from difficulty breathing or swallowing to limbs drawn inward or in a fixed position. Some varieties of the disease can even affect the heart and other organs.

Fortunately, researchers are in the clinical stages of working on a drug designed to better treat Duchenne muscular dystrophy, known as eterplirsen. They believe that participants involved in this therapy could possibly see an increase in the production of a vital protein for muscle growth and health. 

"I've been doing this for more than 40 years and this is one of the most exciting developments we've seen," said Jerry Mendell, MD, lead author of the study and director of the Center for Gene Therapy at Nationwide Children's, via a press release. "It offers great hope to patients with Duchenne muscular dystrophy and their families."

Background information from the study shows that approximately one in every 5,000 male births in the United States have this disorder, which leaves them unable to walk on their own by the age 12. Duchenne muscular dystrophy in particular harms the body's ability to produce a necessary protein known as dystrophin that helps asorb the shock or energy created through muscle contraction. Over time as scar tissue builds up, fat replaces the dead muscle.

The researchers tried to mimic this naturally occurring phenomenon by allowing cells to skip over exon 51 in the dystrophin gene. Participants then received the drug in weekly IVs with one group getting 30 mg/kg dose and another group receiving 50 mg/kg. The control group received a placebo. Each of the participants was asked to complete a six-minute walk test at the beginning of the experiment, followed with muscle biopsies taken at the beginning and throughout interval periods of the study.

The study concludes the following: "Although there was no dystrophin production at 12 weeks, participants showed a 23 percent increase in dystrophin-positive muscle fibers by the 24-week mark. The striking improvement and lack of side effects prompted researchers to switch participants in the placebo group to the drug. By week 48, participants had a 52 percent increase in dystrophin-positive muscle fibers and were able to walk 67.3 meters farther than the placebo group on the six-minute walk test."

And study authors also point out that there will need to be further studies in order to determine how the drug affects dystrophin production in muscles.

"We know that if you have an area that is not expressing dystrophin, the membrane will be fragile and vulnerable to activity-related degeneration," said Dr. Mendell, who also is director of the Neuromuscular Disorders program at Nationwide Children's and a professor of pediatrics in The Ohio State University College of Medicine, via the release. "There may be factors that lead to preferential localization of the dystrophin production. That's one of many issues we'd like to investigate further."

While there is no cure for muscular dystrophy, medications and therapy can slow the course of the disease.

More information regarding the study can be found in the Annals of Neurology.