A progressive, lethal condition with no cure, Duchenne muscular dystrophy (DMD) often diminishes a child's ability to walk during adolescence and typically leads to respiratory failure or cardiomyopathy during their 20s. While many treatment options slow down the progression of disease, there remains no known treatment to stop or reverse DMD. Experts at Nicklaus Children's Hospital hope gene therapy may do just that.

“Gene therapy offers potential for improved outcomes and longevity for families whose loved ones have DMD,” says Migvis Monduy, MD, pediatric neurologist and Medical Director of the Neuromuscular and Movement Disorders Programs at Nicklaus Children's Hospital. “It's not a cure, but it's the best option we have available right now.”

The goal of DMD gene therapy is to sufficiently slow down progression of the disease until it halts altogether. Even when gene therapy meets this lofty goal, it does not allow children to recover lost function. Despite this, preventing further weakness and progression of disease has substantial effect on a child's function and quality of life.

Additional Tool With Positive Results

Developed by Sarepta Therapeutics, ELEVIDYS gained FDA approval in 2023 for ambulatory children ages 4 through 5 with a confirmed mutation in the DMD gene. Accelerated approval was granted in 2024 for ambulatory cases, and therapy is now approved for patients ages 4 and older. The therapy focuses on the dystrophin gene, the genetic source of DMD, sending a shortened dystrophin called ELEVIDYS-dystrophin.

Because the entire dystrophin gene cannot fit in a capsule, the most vital parts of the gene are contained within an adeno-associated virus serotype 9 (AAVRh74) viral capsule. Once in the child's body, the ELEVIDYS-dystrophin helps the child make micro-dystrophin to stabilize muscles and reduce weakness.

Recognizing the potential wielded by this new gene therapy, Nicklaus Children's became one of the first in the nation to offer this innovative therapy soon after the FDA's 2023 approval.

“It's exciting to have treatment options and different tools in our box,” Dr. Monduy says. “Before, we just diagnosed and supported families from a psychological standpoint. Then steroids came along, which brought some hope with a lot of side effects and baggage. Now we're getting to the underlying genetic cause, which is exciting and promising."

The first use of DMD gene therapy reaped positive results for 6-year-old Jacob. When he came to Nicklaus Children's, Jacob could still walk, but he was growing weaker. If he fell, he was too weak to regain his footing on his own. Since receiving genetic therapy at Nicklaus Children's, he has gained the ability to run and jump. A second patient has also experienced positive results of the therapy, which Dr. Monduy hopes will last for years to come.

Finding the Ideal Candidate

The most obvious criterion for genetic therapy is a diagnosis of DMD. Additionally, a child's candidacy requires antibody testing.

“A child who has already been exposed to the delivery virus and has created antibodies against the virus,” Dr. Monduy says, “is not a candidate.”

Assuming a child has not developed antibodies against the delivery virus, further testing takes place. Children with advanced liver or heart disease are also ineligible, as the therapy can be detrimental to their long-term liver or heart health, worsening another chronic condition.

This potential detriment comes not only due to gene therapy, but also from the obligatory subsequent steroid therapy to prevent immune activation that would render gene therapy ineffective. For the first three months following gene therapy, patients undergo weekly monitoring and lab work, and they receive steroids to decrease risk of myocarditis, myositis and liver injury. After three months, the steroids are tapered off and patients continue with their pre-gene therapy steroid regimen.

Eager for Progress in the Race Against Time

In appropriate patients, the current gene therapy offering holds the potential to improve many aspects of daily life. There is, however, ample opportunity for improved therapeutic options. At Nicklaus Children's, many children are awaiting DMD gene therapy currently.

“The good news of this new therapy also comes with heartbreak,” Dr. Monduy says, “as approximately 30 to 40 percent of those who come to us for gene therapy have antibodies that prevent them from being candidates.”

Dr. Monduy hopes additional advances will open the door to more children in need of DMD gene therapy. Future clinical trials will hopefully aid in this, as researchers may use plasmapheresis or other strategies to rid a child's body of antibodies to allow use of ELEVIDYS. In the meantime, Dr. Monduy points out that children with DMD are in a “race against time.”

The race begins the moment they're born. When they come to the multidisciplinary team at Nicklaus Children's, they undergo an evaluation with a multidisciplinary team that includes cardiac and pulmonary function testing, bone health and a nutritional status evaluation. Once the team determines a child is a candidate for gene therapy, the team reaches out to the family's insurance company. Because this is a novel treatment option, it takes a lot of education to convince insurance companies to offer coverage. As a result, some patients wait months to receive their therapy. All the while, the child's health deteriorates.

Speeding up the process begins with earlier diagnoses.

“Historically, we haven't made a dent in early detection and diagnosis of DMD,” Dr. Monduy says. “Now that we have gene therapy, physicians should consider screening for any child with motor delays with CPK. By starting gene therapy at a younger age, we may halt progression of the disease earlier when children still have more strength and motor function and have a different outcome.”