Background: Delandistrogene moxeparvovec is an FDA-approved adeno-associated virus (AAV) mediated gene therapy approved for the treatment of ambulatory individuals with Duchenne Muscular Dystrophy (DMD) aged 4 and older. Patients with DMD-related cardiomyopathy were excluded from participation in clinical trials, and so safety and efficacy in this population is unknown. Known potential side effects of this therapy include early myocardial inflammation due to an immune-mediated response to the viral capsid, as well as later inflammatory response directed at the microdystrophin transgene. Additional information is needed to understand the safety and efficacy of this therapy in patients with DMD-related cardiomyopathy.
Objectives: To describe the unique clinical management and course of a 15-year-old boy with moderate cardiomyopathy treated with delandistrogene moxeparvovec.
Results: We describe the case of an ambulatory 15-year-old boy with DMD as well as concurrent DMD-associated cardiomyopathy. Prior to treatment, echocardiogram showed a left ventricular ejection fraction of 33% and cardiac magnetic resonance imaging revealed left ventricular dilation with myocardial thinning as well as late gadolinium enhancement encompassing 54% of the myocardial mass. Treatment protocol included the use of prophylactic sirolimus in an attempt to reduce immune-mediated adverse events. The patient was treated with gene therapy while inpatient and monitored closely on telemetry due to the risk of post-infusion myocarditis. He tolerated treatment well, with mild nausea and decreased appetite. Daily troponin levels and telemetry monitoring over the first 10 days post infusion remained normal. After discharge, cardiac monitoring was significant for normal weekly troponin levels (apart from one mildly elevated level that resolved quickly) and stable monthly echocardiograms. However, acute liver injury occurred at week 5 post infusion, requiring admission for high dose IV solumedrol twice, as well as addition of mycophenolate mofetil. This ultimately resolved with these immunomodulatory strategies and labs normalized by week 18 post infusion.
Conclusions: This case demonstrates the short-term safety of delandistrogene moxeparvovec in a single DMD patient with moderate cardiomyopathy as demonstrated by decreased ejection fraction and significant cardiac fibrosis. Ongoing monitoring will be performed to understand long term safety as well as efficacy of this therapy.