Asymptomatic troponin I elevation and acute myocarditis in the late period of gene replacement therapy with onasemnogene aberpavovec for patients with spinal muscular atrophy: literature review and clinical case series

Introduction. Spinal muscular atrophy (SMA) 5q is a rare genetically determined progressive neuromuscular disorder, is the most frequent cause of infant death not long ago. Nowadays onasemnogen abeparvovec as pathogenetic therapy is successfully used in clinical practice to combat this disease. Gene replacement therapy (GRT) with onasemnogen abeparvovec for SMA patients may come amid non-target changes in the cardiovascular system that require early diagnosis and monitoring. Objective. To present clinical reports considering children with genetically confirmed SMA and elevated troponin I levels after onasemnogen abeparvovec gene replacement therapy. Materials and methods. We monitored forty two children with genetically confirmed SMA who received gene replacement therapy with onasemnogen abeparvovec in the pediatric neurology department. All patients were tested for troponin I before and after the infusion, additional tests of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), creatine phosphokinase-MB (CPK-MB), electrocardiogram, echocardiography were made if needed. Results. In 11 (26.2%) of 42 SMA children troponin I was elevated and detected up to the eighth week after drug administration. At the same time, an increased concentration of troponin I in the majority of cases (41 out of 42 children) was not associated with clinically significant manifestations. There was only one case when acute myocarditis, confirmed by clinical and instrumental methods of investigation occurred. It was a girl with a long-term (10 months) elevation of troponin I, who had an intercurrent infection. Conclusions. Troponin I elevations detected after GRT with onasomnogene abeparvovec in SMA patients are often asymptomatic. This myocarditis case highlights the importance of longer cardiac monitoring of troponin I elevations, especially in the presence of intercurrent bacterial and viral infections.