Gene therapy in pediatric patients with spinal muscular atrophy in Kazakhstan: Challenges and achievements.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that results from a low level of survival motor neuron (SMN) protein. Onasemnogene abeparvovec is an approved genetic therapy that consists of a viral vector that carries DNA encoding the SMN protein. In this single-center, observational study, we used onasemnogene abeparvovec in pediatric patients with SMA in Kazakhstan. In 2021, we collected data from 10 patients under 2 years of age with SMA types 1 and 2 who received onasemnogene abeparvovec therapy. Post-treatment follow-up was conducted remotely. We analyzed outcomes of the treatment reflected by the changes in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores and patients' survival, as well as adverse events with a focus on aspartate and alanine transaminase levels. The patients' survival rate at 6 months was improved by gene therapy even after 24 months of observation. All patients experienced elevated aminotransferase concentrations after drug infusion. One patient died of liver failure 56 days after infusion, following the ending of corticosteroid treatment, which was probably due to an immunological response to the uptake of the viral vector. Based on our results, prolonging corticosteroid treatment and closely monitoring patients after the drug infusion is advisable. Challenges of remote monitoring should also be addressed for patients who cannot stay in the hospital for extended periods of time. A multidisciplinary approach is important for symptomatic patients, while gene therapy should be the first consideration for pre-symptomatic patients.