The U.S. Food and Drug Administration approved Elevidys in June, making it the first gene therapy designed to halt the progression of pediatric Duchenne muscular dystrophy, a life-threatening genetic disorder of progressive muscular weakness.

The gene therapy involves the stimulation of a microdystrophin gene, which produces a shortened form of dystrophin, about one-third the size. Microdystrophin delivery is then targeted to muscle cells using vectors or adeno-associated viruses (AAVs).

Elevidys will be available to patients ages four to five years, assuming they have no medical complications towards this therapy. An example of a complication that would prevent a patient from being a candidate for Duchenne muscular dystrophy (DMD) gene therapy is if the patient has developed antibodies to the AAV that is used for microdystrophin delivery. The patient’s immune system may respond to the AAV in a way that neutralizes the therapeutic gene’s effect on the body.

Elevidys is not a cure and cannot restore lost muscle function, however, until now there was no treatment to even slow the progression of DMD, which affects one in 3,500 males worldwide. The gene therapy, developed and manufactured by Sarepta Therapeutics, targets the underlying cause of DMD, which makes it unlike previous treatment methods for the disorder.

First identified in the late 19th century, DMD results from mutations in the dystrophin gene which is located on the X chromosome. Because males only have one X chromosome that can be expressed while either of two X chromosomes can be expressed in females, DMD more commonly affects males, while females may be carriers or mildly affected.

In the United States, all forms of muscular dystrophy affects an estimated 250,000 individuals in the United States. The signs and symptoms generally onset between ages three to five.

There are several symptoms associated with DMD, including greater susceptibility to falls, a gait, limitations with physical activities such as running and learning disabilities.

To date, there is no cure for the disorder, but the symptoms can be controlled with physical therapy, the use of assistive devices such as wheelchairs and medication. Corticosteroid drugs like prednisone and deflazacort, also known as anti-inflammatory medications or steroids, have been used to treat patients with DMD. These drugs only slow the progression of muscle weakness in affected individuals and delay the need to walk with assistance by two to three years.

The dystrophin gene mutation that causes DMD results in patients lacking the protein responsible for keeping muscle cells intact. The main consequence of a dystrophin deficiency is muscle damage every time the individual contracts their muscles. This not only affects skeletal and smooth muscle but also cardiac muscle which is responsible for controlling the heart.

Neurologist Jerry Mendell at Nationwide Children’s Hospital in Columbus, Ohio had seen his first patient with DMD over 50 years prior. Mendell, who is also the principal investigator at the Center for Gene Therapy, led the Phase I study of a systemic gene therapy for DMD. “This is what I’ve devoted my life to … The [Food and Drug Administration] FDA’s decision means we can save more function and save the quality of life for these children and their families,” Dr. Mendell said.

Although the FDA has approved the pediatric gene therapy, clinical trials will continue to be conducted until the fall of 2023 to determine the therapy’s effectiveness in interrupting the progression of DMD. Following the initial completion of Sarepta Therapeutics’ Phase 3 EMBARK trial, the goal is to expand the scope of Elevidys gene therapy to treat patients with milder DMD symptoms, regardless of age.

In addition, Sarepta plans to initiate clinical trials with Swiss pharmaceutical company Roche for DMD treatment in males as young as 6 months old. If the trials are successful, the gene therapy’s scope could be expanded to include the administration of the gene therapy in infants, before the onset of muscle damage.

CORRECTION [7/17/23, 10:00 a.m.]: A previous version of this article incorrectly stated that Pfizer, Genethon, and Solid Biosciences aided in the production of the therapy alongside Sarepta Therapeutics. This article has been corrected to reflect that Sarepta alone is responsible for development and manufacturing, and retains exclusive rights to the therapy in the United States. Additionally, the article now makes clear that Elevidys is not a cure and cannot restore lost muscle function, but rather is designed to halt progression of Duchenne’s muscular dystrophy.