Onasemnogene Abeparvovec Treatment after Nusinersen in an Infant with Spinal Muscular Atrophy Type 1

Kurume Med J. 2024 Jan 16. doi: 10.2739/kurumemedj.MS6934008. Online ahead of print.

Abstract

Background: Until recently, the treatment of spinal muscular atrophy (SMA) was limited to symptomatic treatment with no cure. Three innovative drugs, nusinersen, onasemnogene abeparvovec (OA), and risdiplam have been developed to treat SMA. Although the clinical trials for these drugs have demonstrated their efficacy, there is limited information on real world treatment strategies. In this study, we present a case of a male infant with SMA type 1 who underwent OA treatment after nusinersen treatment.

Case presentation: At 4 months of age, the patient was diagnosed with SMA type 1. At 6 months of age, nusinersen treatment was initiated. His motor function improved, but the effect was limited; therefore, his parents requested gene replacement therapy. During the preparation for OA treatment, anti-adeno-associated virus 9 (AAV9) antibody tests repeatedly showed non-specific reactions, which delayed initiation of treatment. The patient was put on ventilator management after he caught a common cold. During this management, the anti-AAV9 antibody test results were negative. Furthermore, the patient showed increased transaminase levels just before OA treatment; however, since these gradually decreased without signs of liver failure, we started OA treatment at 13 months of age. Four months later, the patient began to sit without support and was weaned from non-invasive positive pressure ventilation, although nasogastric tube feeding remained partially necessary.

Conclusion: We believe that the management of unstable SMA type 1 symptoms, anti-AAV9 antibody testing, and changes in transaminase levels will be helpful for other patients with SMA who require treatment.

Keywords: case report; onasemnogene abeparvovec; spinal muscular atrophy type 1; transitional period; treatment.