Clinical Experience of gene replacement therapy in children with Spinal Muscular Atrophy: A single center retrospective study of 25 children

Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder and is the most common genetic cause of infant death. SMA is caused by the deletion or mutation of survival motor neuron 1 (SMN1), which results in the loss of motor neurons in anterior horn cells of the spinal cord. Therapeutic strategies to increase levels of SMN protein in motor neurons have focused on enhancing the effectiveness of SMN2 or replacing the SMN1 gene. Onasemnogene abeparvovec-xioiwas, which is one-time intravenous SMN gene replacement therapy, was approved by FDA in May 2019 for treatment of children less than 2 years of age with SMA type 1. Post marketing studies describing its use for the treatment of SMA are limited especially outside Europe and United States. This is a retrospective study of patients’ characteristics and clinical outcome of 25 children with SMA who received onasemnogene abeparvovec (Zolgensma) in our centre in the UAE, between November 2020 and January 2022. The following data were collected as available: age at diagnosis, SMA type, genetic information, respiratory status, prior treatments, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) at baseline, 1 and 3 months post therapy, adverse events, and laboratory values. This study demonstrates that onasemnogene abeparvovec is well tolerated in SMA patients. Significant improvements in CHOP INTEND scores were observed at 3months following therapy versus baseline (P-Value < 0.005). Transiently elevated liver enzymes and transient thrombocytopenia were the common side effects. There were no life-threatening side effects noted.
Keywords: spinal muscular atrophy , Gene therapy , Onasemnogene abeparvovec