Real-World Data in Children with Spinal Muscular Atrophy Type 1 on Long-Term Ventilation Receiving Gene Therapy: A Prospective Cohort Study.

Abstract

Patients with spinal muscular atrophy type 1 (SMA-1) requiring invasive ventilation can be eligible for gene therapy if they tolerate at least 8 h off ventilation per day. We aimed to assess the short-term safety and efficacy of gene therapy (onasemnogene abeparvovec; Zolgensma) on respiratory function in SMA-1 patients ventilated via tracheostomy pre-gene therapy. A prospective cohort study included 22 patients. Patients were weaned off ventilation for at least 8 h daily by optimizing ventilator settings and duration, using cough augmentation, managing excessive airway secretions, enhancing nutrition, screening for respiratory bacterial colonization, and treating infections. Gene therapy was administered at a median age of 26 (Q1: 18, Q3: 43) months with a mean follow-up period of 7.64 (SD: 6.50) months. Gene therapy was safe and effective in resolving paradoxical breathing, improving cough ability, reducing airway secretions, and enhancing CHOP-INTEND scores. The clinical assessment and management implemented pre-gene therapy were effective in safely weaning patients for at least 8 h off ventilation daily. Gene therapy at a late age was safe and effective over the short-term period; however, long-term follow-up is recommended. In conjunction with gene therapy, high-quality clinical care is beneficial and should be paired with gene therapy.