In the 1960s, Dr. Jerry Mendell encountered his first patient with Duchenne muscular dystrophy, a genetic disorder that results in the progressive weakening of muscles. Fast forward more than 50 years later, and Mendell has developed the first treatment that can slow down the progression of the disease. Duchenne is caused by a mutation in the dystrophin gene, which is responsible for producing a protein necessary for healthy muscle function. Symptoms typically start to appear in children between the ages of 3 and 6, and worsen over time, eventually leading to breathing difficulties and heart problems as well as loss of muscle control.
While gene therapy to replace the faulty gene is the most effective solution for Duchenne, it has been challenging to find a way to deliver a healthy copy of the gene into cells. Due to its size, dystrophin is one of the largest genes in the body, making transport into cells a complex task. Mendell’s research focused on a related muscle disorder where individuals with slightly different mutations in dystrophin were still able to maintain healthy muscle function and a relatively normal life. This led Mendell to collaborate with Sarepta Therapeutics to develop a way to deliver the crucial parts of the gene to patients with Duchenne.
The gene therapy developed by Mendell and his team was approved by the U.S. Food and Drug Administration in June 2023. The first group of young boys treated with the therapy have shown promising results, with their bodies producing healthier copies of dystrophin and not experiencing the typical symptoms of the disease such as muscle weakness. Mendell, now a senior adviser at the Center for Gene Therapy at Nationwide Children’s Hospital, believes that this is just the beginning and there is still more work to be done to perfect gene therapy for Duchenne.