Evaluation of cardiac function in patients with SMA after treatment with onasemnogene abeparvovec.

Background: Spinal muscular atrophy (SMA) is a recessively inherited neurological disease resulting in motor neuron disorder. Onasemnogene abeparvovec is a gene replacement therapy used to treat patients with SMA. Cardiac toxicity was observed in animal studies on this therapy, and elevated cardiac troponin I levels were observed in clinical trials; however, the clinical importance of these findings is unknown. Therefore, this study aimed to reveal the cardiac toxicity of onasemnogene abeparvovec through careful investigation of cardiac function using cardiac strain analysis, which can detect early subtle abnormalities.

Methods: This study included patients with SMA treated with onasemnogene abeparvovec between June 2020 and November 2020. Echocardiography, including peak global longitudinal strain (GLS), and other laboratory test results were evaluated.

Results: Case 1 showed a relative GLS decrease of 14.5% compared with that at the baseline (GLS reduction from -22.1% to -18.9%), elevation of N-terminal prohormone B-type natriuretic peptide levels from 227 pg/mL to 494 pg/mL, and elevated liver enzyme concentrations after gene replacement therapy without reduction of the left ventricular ejection fraction.

Conclusions: Subclinical myocardial dysfunction after infusion of onasemnogene abeparvovec was suggested by careful investigation of cardiac function. Cardiac toxicity may correlate with liver impairment following gene replacement therapy. Long-term studies that allow for a higher number of patients and more extended observation periods should be conducted to confirm the cardiac toxicity of onasemnogene abeparvovec.