Gene therapy benefits in a small cohort of symptomatic 5q spinal muscular atrophy patients and real world pediatric outcomes

Abstract

OBJECTIVE: To characterize clinical outcomes of gene replacement therapy administered after symptom onset in a small group of children with 5q spinal muscular atrophy (SMA) and to describe its impact on motor function and supportive care needs in real-world practice. METHODS: Observational cohort study with retrospective and prospective data collection at a single pediatric center. Children with molecularly confirmed type 1 or type 2 5q SMA who received onasemnogene abeparvovec and remained in multidisciplinary follow-up were consecutively included. Due to the small sample (n = 7) and patient heterogeneity, analysis was exclusively descriptive. RESULTS: Seven symptomatic children were evaluated (six type 1, one type 2). After treatment, motor milestones showed localized improvements; all type 1 patients achieved head control and sitting with support, and 83.3% achieved independent sitting. The type 2 patient achieved independent ambulation. Adverse events occurred in 85.7% of patients and were mostly mild to moderate, though one case of thrombotic microangiopathy required dialysis with favorable recovery. Despite motor gains, prior and simultaneous use of other therapies (nusinersen, risdiplam) acted as confounding factors, and most children remained dependent on noninvasive ventilation and gastrostomy. CONCLUSIONS: In this small and heterogeneous cohort, gene therapy after symptom onset was primarily associated with clinical stabilization and limited motor milestone acquisition, while established respiratory and nutritional impairments persisted. These results emphasize the need for realistic treatment counseling and reinforce the importance of early diagnosis.