New hope for patients with Duchenne muscular dystrophy

A study conducted by a team of researchers from The Research Institute at Nationwide Children’s Hospital, shows that eteplirsen can improve walking performance of patients with Duchenne muscular dystrophy. This is the first study to demonstrate that an exon-skipping drug increases the production of dystrophin, a protein essential for muscle growth and health. The study, which was published in the journal Annals of Neurology, is an important progress in muscular dystrophy research.

Duchenne muscular dystrophy is the most common form of muscular dystrophy in children, affecting approximately 1 in 5000 births of boys in the United States. Duchenne muscular dystrophy is a debilitating disease that affects the muscles; at 12 years, most patients end in a wheelchair. This disorder occurs due to a mutation in the DMD gene that encodes a protein called dystrophin. Without this protein, the muscle can no longer contract, and muscle fiber gradually degenerates and are replaced by scar tissue and fat.

Jerry Mendell, MD, lead author of the study and director of the Center for Gene Therapy at Nationwide Children’s, said they have been working on this research for over 40 years and it is one of the most exciting discoveries he has seen. He added that this finding offers hope for patients with Duchenne muscular dystrophy and for their families.

Researchers at The Research Institute at Nationwide Children’s Hospital conducted a double-blind, randomized study to test the efficacy of eteplirsen, an exon-skipping drug. They were able to show that this drug can improve motor performance of patients with Duchenne muscular dystrophy in a standard 6-minute test drive. It was a phase 2 clinical trial that included 12 boys aged between 7 and 12 years, who received weekly 30 mg / kg or 50 mg / kg of eteplirsen. Compared with the placebo group, participants who received eteplirsen had an increase of 23% in dystrophin production at week 24. Due to this significant improvement and lack of adverse effects, researchers included the participants from the placebo group in the drug group. Furthermore, at week 48, there was a 52% increase in dystrophin-positive muscle fibers and, at the 6-minute walk test, the participants were able to walk 67.3 meters farher than the placebo group.

More than half of the patients with DMD dystrophin gene lack large sections of DNA called exons, which contain the instructions for making proteins. Eteplirsen is an exon-skipping drug that allows the cells to skip these regions of DNA, namely across exons. “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, “said Dr. Mendell.