Gene therapy in spinal muscular atrophy

Infantile SMA is a neuromuscular disease caused by the motor neuron degeneration, depending on the age of appearance of clinical signs and the evolution of the disease, three types of decreasing severity have been defined. SMA is caused by mutations or deletions of the SMN1 gene and disease. Various therapies aimed at increasing SMN protein levels have been developed. Gene therapy is part of the therapeutic arsenal now available for the treatment of SMA under certain conditions. It uses the scAAV9 vector carrying a functional copy of SMN1 to restore SMN protein expression at the cellular level. Because the adeno-associated virus genome is maintained as it is an episome, a single intravenous administration is sufficient to producing a long-lasting therapeutic effect. The effectiveness of gene replacement therapy in patients with SMA has been demonstrated in various studies. It is now clear that treatment as early as possible provides better clinical results. However, this treatment must be carried out in a suitable medical environment, with close monitoring initially due to potentially serious side effects. In France, this treatment has been available since 2019. A national committee of experts involved in the treatment of pediatric SMA patients has established that pediatric patients with SMA decide on the indications for disease-modifying therapies (DMT) in children. The French Spinal Muscular Atrophy Registry (SMA France Registry) was established in January 2020. The registry includes all patients with genetically confirmed SMN1-related SMA. All patients treated with GT are systematically included in the registry. As of July 21, 2023: 72 patients with SMA have been treated with GT in France since June 2019. The arrival of new treatments reveals new clinical phenotypes of SMA which constitute a new management challenge. Treatment as early as possible is also a very important factor for a favorable outcome and calls for presymptomatic screening. However, the arrival of these new treatments, extremely expensive raises other socio-economic questions. © 2023 Published by Elsevier Masson SAS on behalf of French Society of Pediatrics.