First Approved Gene Therapy for Muscular Dystrophy Brings Hope to Kids Everywhere
Jerry Mendell, MD, has dedicated his 50-year career to understanding and treating Duchenne muscular dystrophy, the most common form of muscular dystrophy that begins with muscle weakness in childhood and progresses to heart and lung failure in early adulthood. Mendell and his team developed a gene therapy to correct the cell function of those with the disease. That gene therapy has been approved by the FDA.
Newswise — (COLUMBUS, Ohio) – Today, the Abigail Wexner Research Institute at Nationwide Children’s Hospital praised the Food and Drug Administration (FDA) for its accelerated approval of SRP-9001/ELEVIDYS for Duchenne muscular dystrophy (DMD) following decades of research in its Center for Gene Therapy to help patients with neuromuscular diseases.
The FDA approved the treatment for pediatric patients 4-5 years old with DMD. Jerry Mendell, MD, principal investigator in the Center for Gene Therapy at the Abigail Wexner Research Institute, led the first Phase I study of a systemic gene therapy for DMD. Dr. Mendell saw his first patient with DMD more than 50 years ago, igniting his passion to develop new treatments for patients with neuromuscular diseases.
“This is what I’ve devoted my life to; since I began investigating gene therapy as a potential treatment for children with neuromuscular disorders, it’s been my dream to develop a gene therapy for DMD,” Dr. Mendell said. “The FDA’s decision means we can save more function, and save the quality of life for these children and their families.”
Duchenne muscular dystrophy is a severe form of muscular dystrophy caused by a mutation in the DMD gene, resulting in a lack of the dystrophin protein, leading to muscle weakness and atrophy. Muscle weakness may affect the skeletal muscle and the heart muscle. As an X-linked condition, DMD typically affects boys and is progressive; over time, children with DMD develop problems with walking, breathing and heart function.
SRP-9001 is a novel DMD gene-replacement therapy co-invented by Dr. Mendell and Louise Rodino-Klapac, PhD, formerly at Nationwide Children’s and currently the executive vice president, head of Research and Development, and chief scientific officer at Sarepta Therapeutics. This gene therapy program was licensed by Sarepta in 2018. The therapy, an intravenous infusion of ELEVIDYS, packages a micro-dystrophin gene into an adeno-associated virus serotype (AAVrh74, which was isolated at Nationwide Children’s) to deliver missing or corrected genes to cells.
SRP-9001-101, the first Phase I study, targeted study participants 4 to 7 years, the age range when symptoms start showing. Participants were followed for five years. Across three independent SRP-9001 studies, meaningful and statistically significant improvement in North Star Ambulatory Assessment (NSAA) scores were seen, including a nearly 10-point improvement among boys treated in SRP-9001-101. NSAA is a 17-item scale that evaluates how well a child can perform a range of functions, including walking, running and getting up from a reclined or lying position.
As an international leader in pediatric research, Nationwide Children’s is actively involved in more than 2,500 clinical research projects to transform health. In the gene therapy space, researchers at Nationwide Children’s also led the Phase I clinical trial that was the first to study gene therapy for spinal muscular atrophy type 1 (SMA1), the most severe form of SMA. This seminal research performed at Nationwide Children’s led to the development and 2019 FDA approval of Zolgensma® for SMA.
“Nationwide Children’s Center for Gene Therapy is a national leader in gene therapy with a robust pipeline of gene therapies in development for numerous genetic conditions in various stages of research,” said Kevin Flanigan, MD, director of the Center for Gene Therapy. “The Abigail Wexner Research Institute’s investment in a clinical trial infrastructure, a Good Manufacturing Practice (cGMP) facility, regulatory experts and an Office of Technology Commercialization continues to help us advance treatments from the bench to the bedside.”
The preclinical work leading to the FDA approval of ELEVIDYS was conducted by researchers from Nationwide Children’s. In a key milestone toward advancing the research, faculty member Scott Harper, PhD, first described the micro-dystrophin gene in a 2002 Nature publication, prior to his arrival to Nationwide Children’s.
Sarepta Therapeutics is a global biotechnology company developing genetic medicine for rare diseases. Funding for the initial trial was partially provided by Parent Project Muscular Dystrophy and Sarepta Therapeutics. Nationwide Children’s has received licensing and milestone payments as a result of the licensing agreement with Sarepta and will benefit from royalties. Commercialization revenue is reinvested into all research programs across the Abigail Wexner Research Institute at Nationwide Children’s.
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About The Abigail Wexner Research Institute at Nationwide Children's Hospital Named to the Top 10 Honor Roll on U.S. News & World Report’s 2023-24 list of “Best Children’s Hospitals,” Nationwide Children’s Hospital is one of America’s largest not-for-profit free-standing pediatric health care systems providing unique expertise in pediatric population health, behavioral health, genomics and health equity as the next frontiers in pediatric medicine, leading to best outcomes for the health of the whole child. Integrated clinical and research programs are part of what allows Nationwide Children’s to advance its unique model of care. As home to the Department of Pediatrics of The Ohio State University College of Medicine, Nationwide Children’s faculty train the next generation of pediatricians, scientists and pediatric specialists. The Abigail Wexner Research Institute at Nationwide Children’s Hospital is one of the Top 10 National Institutes of Health-funded free-standing pediatric research facilities in the U.S., supporting basic, clinical, translational, behavioral and population health research. The AWRI is comprised of multidisciplinary Centers of Emphasis paired with advanced infrastructure supporting capabilities such as technology commercialization for discoveries; gene- and cell-based therapies; and genome sequencing and analysis. More information is available at NationwideChildrens.org/Research.
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