In a new case report, a team of clinicians and researchers from Children’s Hospital of Philadelphia (CHOP) describe a serious adverse event when delivering an FDA-approved gene therapy for Duchenne muscular dystrophy (DMD) along with the follow up care and research performed to improve the patient’s outcome and better understand the mechanism of the event. The findings were published today in the New England Journal of Medicine.
DMD is the most common childhood muscular dystrophy, caused by a faulty dystrophin gene which normally helps protect muscle. Without dystrophin, muscles are gradually damaged and replaced by fat and scar-like tissue, leading many children to lose the ability to walk by the early teen years and later develop serious heart and breathing problems. In DMD patients, life expectancy varies with genetics and access to coordinated specialty care.
The FDA first approved the gene therapy Elevidys (delandistrogene moxeparvovec-rokl) for DMD in 2023. Since DMD stems from a single gene defect, the gene therapy aims to correct this defect and help the body produce a shortened but working form of dystrophin (micro-dystrophin). While this approach is not a cure and cannot replace muscle already lost, it may slow decline and potentially improve strength and endurance – making studies essential to understand its benefits and associated safety, especially in the heart.
This case report emphasizes that, as with many first-in-class gene therapies, there are still important areas for continued study after such products are marketed. In this case, particular areas for continued study include how much micro-dystrophin is produced in the human heart, how uniformly it is expressed, and how those factors relate to both benefit and risk.
“In DMD, where cardiac involvement is a major driver of long-term outcomes, understanding cardiac expression and monitoring short and long-term cardiac effects of the therapy is critical,” said Lindsey George, MD, the study’s senior author, CHOP’s Director of Clinical In Vivo Gene Therapy and an attending physician in the Division of Hematology.
In the report, researchers describe a 17-year-old patient with DMD who experienced significant cardiac toxicities after receiving the Elevidys gene therapy. These included early myocarditis with symptomatic atrial fibrillation at Day 2 and later recurrence of cardiac injury signals with worsening heart function around Day 42, prompting escalation to high-dose intravenous steroids to address the symptoms and diagnostic tissue evaluation.
Clinicians conducted close surveillance of cardiac status and lab markers beyond that indicated in the product labeling and thus were able to treat the patient’s inflammatory episodes promptly. Because of clinical concern, the treatment team obtained endomyocardial (heart) and skeletal muscle (biceps) tissue as part of medical care. In addition to the clinical analysis, they then performed molecular analyses to better characterize distribution and expression of the therapeutic donor gene, microdystrophin.
The authors state that even though this report is of a single patient, it suggests that clinicians treating patients with Elevidys may consider additional safety checks that go beyond current product labeling. The authors also said that additional larger studies of the observed modest expression of microdystrophin in cardiac and skeletal tissue from this treatment are necessary to understand if the results are generalizable.
“Delivering state-of-the-art DMD gene therapy requires a multidisciplinary team working in a tightly integrated system to optimize safety monitoring, interpret complex signals and manage side effects effectively,” said Ben Samelson-Jones, MD, PhD, the study's lead author and CHOP's Associate Director of Clinical In Vivo Gene Therapy.
Samelson-Jones et al. “Cardiac Toxicity and Molecular Efficacy after Delandistrogene Moxeparvovec Gene Therapy for Duchenne Muscular Dystrophy.” NEJM. July 22, 2026. DOI: 10.1056/NEJMc2518477
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In a new case report, a team of clinicians and researchers from Children’s Hospital of Philadelphia (CHOP) describe a serious adverse event when delivering an FDA-approved gene therapy for Duchenne muscular dystrophy (DMD) along with the follow up care and research performed to improve the patient’s outcome and better understand the mechanism of the event. The findings were published today in the New England Journal of Medicine.
DMD is the most common childhood muscular dystrophy, caused by a faulty dystrophin gene which normally helps protect muscle. Without dystrophin, muscles are gradually damaged and replaced by fat and scar-like tissue, leading many children to lose the ability to walk by the early teen years and later develop serious heart and breathing problems. In DMD patients, life expectancy varies with genetics and access to coordinated specialty care.
The FDA first approved the gene therapy Elevidys (delandistrogene moxeparvovec-rokl) for DMD in 2023. Since DMD stems from a single gene defect, the gene therapy aims to correct this defect and help the body produce a shortened but working form of dystrophin (micro-dystrophin). While this approach is not a cure and cannot replace muscle already lost, it may slow decline and potentially improve strength and endurance – making studies essential to understand its benefits and associated safety, especially in the heart.
This case report emphasizes that, as with many first-in-class gene therapies, there are still important areas for continued study after such products are marketed. In this case, particular areas for continued study include how much micro-dystrophin is produced in the human heart, how uniformly it is expressed, and how those factors relate to both benefit and risk.
“In DMD, where cardiac involvement is a major driver of long-term outcomes, understanding cardiac expression and monitoring short and long-term cardiac effects of the therapy is critical,” said Lindsey George, MD, the study’s senior author, CHOP’s Director of Clinical In Vivo Gene Therapy and an attending physician in the Division of Hematology.
In the report, researchers describe a 17-year-old patient with DMD who experienced significant cardiac toxicities after receiving the Elevidys gene therapy. These included early myocarditis with symptomatic atrial fibrillation at Day 2 and later recurrence of cardiac injury signals with worsening heart function around Day 42, prompting escalation to high-dose intravenous steroids to address the symptoms and diagnostic tissue evaluation.
Clinicians conducted close surveillance of cardiac status and lab markers beyond that indicated in the product labeling and thus were able to treat the patient’s inflammatory episodes promptly. Because of clinical concern, the treatment team obtained endomyocardial (heart) and skeletal muscle (biceps) tissue as part of medical care. In addition to the clinical analysis, they then performed molecular analyses to better characterize distribution and expression of the therapeutic donor gene, microdystrophin.
The authors state that even though this report is of a single patient, it suggests that clinicians treating patients with Elevidys may consider additional safety checks that go beyond current product labeling. The authors also said that additional larger studies of the observed modest expression of microdystrophin in cardiac and skeletal tissue from this treatment are necessary to understand if the results are generalizable.
“Delivering state-of-the-art DMD gene therapy requires a multidisciplinary team working in a tightly integrated system to optimize safety monitoring, interpret complex signals and manage side effects effectively,” said Ben Samelson-Jones, MD, PhD, the study's lead author and CHOP's Associate Director of Clinical In Vivo Gene Therapy.
Samelson-Jones et al. “Cardiac Toxicity and Molecular Efficacy after Delandistrogene Moxeparvovec Gene Therapy for Duchenne Muscular Dystrophy.” NEJM. July 22, 2026. DOI: 10.1056/NEJMc2518477
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