A Promising Gene Therapy for Older Children with Duchenne Muscular Dystrophy
Article Summary
- A new gene therapy, ELEVIDYS, has been approved to treat older Duchenne muscular dystrophy patients.
- Dr. Roberto Lopez-Alberola is encouraged by the therapy’s impact on a 15-year-old young woman who is a patient of his.
- Dr. Lopez-Alberola hopes Duchenne muscular dystrophy interventions can eventually happen earlier, to circumvent the muscle loss that accompanies the disease.
A new gene therapy, ELEVIDYS, has been approved to treat older Duchenne muscular dystrophy (DMD) patients.
UHealth—University of Miami Health System and Holtz Children’s Hospital physicians are playing a major role in getting them access.
The therapy delivers a functional micro-gene to muscle cells, potentially arresting DMD progression and, in some cases, possibly reversing it.
ELEVIDYS received accelerated FDA approval in 2023, but the therapy could only be administered to children ages 4 and 5. In June 2024, the FDA expanded access to people older than 4.
“I have been working in neurogenetics for 30 years, and it’s amazing to see the dream of gene therapy being realized,” said Roberto Lopez-Alberola, M.D., associate professor of neurology and pediatrics and chief of pediatric neurology at the University of Miami Miller School of Medicine and a neurologist at Holtz Children’s Hospital at Jackson Memorial Medical Center. “It’s a wonderful opportunity to treat these patients and see the impact it’s having. There is much to celebrate.”
Solving a Thorny Biological Problem
DMD is a childhood muscular disorder driven by mutations in dystrophin, a gene that protects muscle cells from damage. Without a functioning gene, children experience progressively worsening muscle weakness that can limit walking, breathing, blood flow and other functions. Until now, treatment options have been limited.
ELEVIDYS uses a harmless virus, AAVrh74, to deliver therapeutic DNA to muscle cells. However, viruses are like suitcases. Scientists can only stuff them so full, and dystrophin is one of the largest human genes. To overcome the size problem, ELEVIDYS uses a micro-dystrophin that can both fit inside the virus and, hopefully, provide therapeutic benefit.
Siblings Raniya, who is 15 years old, and Amir, 8, received their single ELEVIDYS infusions at Holtz Children’s Hospital in late October. Raniya was the first female ever treated with ELEVIDYS. They may have to wait several months to learn if the treatment was successful, but early signs are encouraging.
“At her recent appointment, Raniya was already doing better, feeling stronger, walking more and not relying on a wheelchair as much,” said Dr. Lopez-Alberola.
Both have experienced side effects and must be monitored closely. While the infusion process is relatively simple, patients must be immunosuppressed to ensure their immune response does not destroy the therapeutic virus.
Clinical trials have shown the drug can improve motor function, particularly in younger children. Because DMD is a progressive disease, older patients often have more muscle damage, a heavy lift for any therapy.
“The worst-case scenario is that some patients do not regain any function,” said Dr. Lopez-Alberola. “However, we may slow the disease’s progression. That alone would be transformational.”
A DMD Journey
Raniya, Amir and their mom, Tannika Scott, travel frequently to Miami from their home in Naples, Florida, for exams and treatments. Dr. Lopez-Alberola has been Raniya’s neurologist for nearly a decade.
“He’s always there to answer my questions, my emails, no matter what he’s doing,” said Scott. “I feel like he’s just a great doctor.”
Scott cannot forget the moment Raniya was first suspected of having DMD. Raniya was 4 and Scott thought she might have diabetes. Tests were negative, but there was definitely something wrong.
DMD wasn’t likely. Dystrophin lives on the X chromosome. Since women have two, mutations would have to damage both gene copies.
Unfortunately, Scott has a family history of DMD. Tests revealed Raniya has the disease. Amir was subsequently diagnosed as well.
The disease has been hard on the family. Scott must perform extra tasks to care for her children, such as toting Raniya’s wheelchair. Raniya must deal with her disease while navigating high school.
“I think the hardest challenge for me is to see them fall, and they get very aggravated and upset,” said Scott. “It’s really hard for Raniya because she doesn’t have people going through the same thing she is going through.”
Waiting and Hoping
Dr. Lopez-Alberola hopes the FDA will continue to extend the age envelope for ELEVIDYS. He envisions a time when infants can be screened and treated in their first weeks of life.
“Right now, we can’t treat until patients become symptomatic,” he said. “By then, some muscle has already been irreversibly lost. It would be much better if we could circumvent the natural history of the disease and prevent that from happening.”
A few weeks out from the infusion, Scott is hopeful this groundbreaking therapy will help her children stave off, and possibly even roll back, the disease.
“At first, I was scared and nervous about it,” said Scott, “but I did my research, and I felt like, if it works, it works. If it doesn’t, then at least I know I tried. I’m just hoping it does work and that my kids can try to live a normal life.
Tags: Department of Pediatrics, gene therapy, muscular dystrophy, pediatrics, Roberto Lopez Alberola