Spinal presentations in children with spinal muscular atrophy type 1 following gene therapy treatment with onasemnogene abeparvovec - The SMA REACH UK network experience

Abstract

Spinal muscular atrophy (SMA) is a neuromuscular disorder of mainly early onset and variable severity. Prior to the introduction of disease modifying therapies (DMTs), children with SMA type 1 typically died before 2 years of age and management was primarily palliative. Onasemnogene abeparvovec (OA), nusinersen, and risdiplam are novel DMTs which ameliorate the effects of the underlying genetic defect at least partially making SMA a treatable condition. Survival and achievement of previously unmet developmental milestones result in treated SMA type 1 children spending more time upright than expected based on the natural history of the treatment-naïve condition. Consequently, spinal asymmetry and kyphosis, features not typically seen in untreated SMA type 1 children due to early mortality, are increasingly common complications. Precise data regarding their prevalence, severity, and management are currently limited. This study describes the spinal features and management in 75 children with SMA type 1 who received OA between March 2021 and December 2022. Retrospective analysis from SMA REACH UK data showed that 44/75 (59 %) clinically had spinal asymmetry and 37 (49 %) had kyphosis. This study aims to raise awareness of this important feature as part of the changed natural history of SMA type 1 post OA treatment.

Keywords: Gene therapy; Kyphosis; Natural history; SMA; Scoliosis; Spinal asymmetry.