Gene-Based Therapy for the Treatment of Spinal Muscular Atrophy Types 1 and 2 : A Systematic Review and Meta-Analysis

Abstract

Abstract Background: Despite numerous studies identifying the advantages of therapies for spinal muscular atrophy (SMA), healthcare professionals encounter obstacles in determining the most effective treatment. This study aimed to investigate the effects of gene-based therapy for SMA. Objective : Methods: A systematic search was conducted from inception to November 2022 across databases. All studies assessing the effects of gene-based therapy on patients with SMA types 1 and 2 were included. The outcomes measured were survival, the need for ventilatory support, improvements in motor function, and the occurrence of adverse drug reactions. Meta-analyses were performed using a random-effects model (PROSPERO registration number: CRD42021284231) Results:A total of 42 studies (n = 1932) were included. The meta-analyses revealed that onasemnogene abeparvovec showed the highest survival rate (95% [95% CI: 88, 100]), followed by risdiplam (87% [95% CI: 77, 95]) and nusinersen (60% [95% CI: 50, 70]). The number of patients needing ventilatory support was reduced after treatment with onasemnogene abeparvovec (risk ratio = 0·10 [95% CI: 0·02, 0·53]). Onasemnogene abeparvovec and risdiplam had similar proportions of patients with improvements in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders score of ≥4 points (92% [95% CI: 62, 100] vs 90% [95% CI: 77, 97]). In contrast, nusinersen had the smallest improvement (75% [95% CI: 66, 83]). The most frequently observed adverse drug reactions were headaches, vomiting, and gastrointestinal disorders. Conclusion: Gene-based therapy benefits patient survival and improves motor function. Onasemnogene abeparvovec and risdiplam appear highly effective, whereas nusinersen exhibits moderate effectiveness.