Effect of nusinersen after three years of treatment in 61 young children with SMA type 1 or 2: a French real-life observational study

Abstract Background Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disorder due to an autosomal recessive mutation in the survival motor neuron 1 gene (SMN1) causing degeneration of the anterior horn cells of the spinal cord and resulting in muscle atrophy. The aim of this paper is to report a 36-month follow-up of children with SMA treated with nusinersen before the age of 3 years. Change in motor function, nutritional and ventilatory support and orthopedics outcomes were evaluated at baseline and 36 months after intrathecal nusinersen and correlated with SMA type and SMN2 copy number. Results We report 88% of the patients who have gained new motor skills during the 3-years period, reaching standing without help and walking with help for 12/37 and 10/37 patients harboring 3 SMN2 copies respectively. No patients with 2 copies SMN2 can stand alone or walk. Patients bearing 3 copies of SMN2 are also more likely to be preserved from respiratory, nutritional and orthopedic complications than patients with 2 SMN2 copies. Conclusion Eventhough SMA patients improve with nusinersen, a lower number of SMN2 gene copies remains a predictor a of poorer evolution under treatment.