Consensus on the use of intrathecal gene therapy for spinal muscular atrophy.

Abstract

Background: Intrathecal (IT) delivery of gene therapy is an emerging strategy for Spinal Muscular Atrophy (SMA), aiming to enhance central nervous system targeting while potentially reducing systemic exposure. The new administration route of Onasemnogene abeparvovec is associated with a distinct safety profile, including dorsal root ganglia toxicity, and requires structured monitoring beyond existing intravenous guidelines, including planning for long-term multidisciplinary follow-up in pediatric and adult care as well as structured transition protocols.

Methods: We expanded the existing intravenous monitoring guideline by incorporating surveillance for potential dorsal root ganglia-related adverse effects. The protocol integrates clinical, laboratory, electrophysiological, imaging, and long-term follow-up recommendations.

Results: The protocol defines pre-treatment assessment, peri-procedural management, and longitudinal follow-up in both pediatric and adult care settings, with emphasis on proactive evaluation of dorsal root ganglia function and structured transition of adolescents treated before adulthood to specialized multidisciplinary adult neurology services.

Conclusions: A structured, multimodal monitoring approach-including dorsal root ganglia surveillance, multidisciplinary long-term follow-up, and coordinated transition from pediatric to adult care-is essential for the safe implementation of intrathecal Onasemnogene abeparvovec in SMA.