In 2023, the Food and Drug Administration (FDA) approved the first gene therapy for Duchenne muscular dystrophy (DMD). This much-needed treatment may slow or stop the progression of this debilitating and deadly disorder. Nicklaus Children’s Hospital is at the forefront of this advancement in care as one of the first hospitals in the U.S. and one of only three in Florida to offer gene therapy for DMD.

An Intractable Disorder

DMD occurs due to a mutation in the DMD gene, which contains the coding for the protein dystrophin, an essential ingredient for muscle function. The mutation prevents dystrophin production in the muscles, leading them to deteriorate. Although cases of DMD without a known family history are common, this is an inherited disorder that affects only boys. Prevalence estimates vary, ranging from approximately 1 in every 3,300 boys to 1 in every 5,000.

Delayed motor development, muscle weakness and wasting in the lower extremities, and other symptoms typically appear before age 6 and progress rapidly. Eventually, many patients are unable to walk without assistive devices, and most require a wheelchair by age 12.

For most patients, challenges continue into young adulthood. Many patients develop skeletal issues. Cardiac and respiratory muscles may weaken, leading to complications, such as cardiomyopathy and pulmonary disorders, which can prove fatal.

DMD lacks a cure, so most treatments seek to mitigate symptoms and complications. Gene therapy, on the other hand, addresses the genetic cause, which is why the recent approval of the recombinant gene therapy ELEVIDYS was a watershed moment for patients, caregivers and clinicians.

Enter ELEVIDYS

Developed by Sarepta Therapeutics, ELEVIDYS uses an adeno-associated virus (AAV) vector called AAVrh74 to deliver a smaller, working version of the dystrophin gene to muscle cells. The DMD gene is one of the largest researchers have found in the human genome, so the developers of ELEVIDYS had to reduce the size of the new version to allow it to fit in the vector. The functional dystrophin gene prompts the muscle cells to produce a truncated version of dystrophin called ELEVIDYS micro-dystrophin.

ELEVIDYS is approved for ambulatory children ages 4 and 5 with DMD and a confirmed DMD gene mutation. The FDA granted accelerated approval for the treatment based on the increased ELEVIDYS micro-dystrophin expression in children who received ELEVIDYS during a randomized clinical trial. The agency found the data “demonstrated that an increase in this surrogate endpoint (expression of ELEVIDYS micro-dystrophin) is reasonably likely to predict clinical benefit” in children who meet the criteria.

The Nicklaus Children’s Brain Institute began offering ELEVIDYS to eligible patients shortly after the therapy received FDA approval.

“At Nicklaus Children’s, we always seek the latest, emerging treatments to support children with complex disorders,” says Migvis Monduy, MD, a pediatric neurologist and Medical Director of the Neuromuscular and Movement Disorders programs. “It is our hope this treatment will delay or halt the progression of DMD for eligible children and offer them brighter tomorrows.”

One-Time Infusion 

Before patients can receive ELEVIDYS, which is administered as a single intravenous infusion, we perform a blood test to measure each patient’s level of anti-AAVrh74 antibodies. If the level is elevated, the patient is not a suitable candidate for ELEVIDYS because the antibodies could attack the vector. Eligible patients must be up to date with recommended vaccinations and have tests of their platelet counts, liver function and troponin-I levels. Patients with a deletion in exon 8 or exon 9 in the DMD gene are not candidates for ELEVIDYS.

Each patient begins a specially designed oral corticosteroid regimen prior to ELEVIDYS administration to help protect against a potential immune response related to treatment. This regimen supplements any corticosteroids patients are already taking.

The single-dose intravenous infusion of ELEVIDYS is simple and straightforward. The treatment typically takes one to two hours. Patients continue to follow the treatment-related corticosteroid regimen for at least three months after receiving ELEVIDYS, and we direct them how and when to taper and halt the medication. For at least three months after treatment, we see patients for weekly testing to monitor their platelet counts, liver function and troponin-I levels.

We advise caregivers to contact us if their child experiences any side effects following ELEVIDYS administration. These may include nausea, vomiting, acute liver injury, pyrexia and thrombocytopenia. 

Nicklaus Children’s is pleased to offer ELEVIDYS to eligible patients from throughout the state of Florida and beyond as we continue to embrace innovative treatments with the goal of extending life and improving the quality of life for children with DMD.

For more information about gene therapy for DMD at Nicklaus Children’s, email a physician liaison at Nicklaus Children’s.