Evaluating the respiratory health of children with spinal muscular atrophy (SMA) type 1 on Nusinersen

Background: Spinal muscular atrophy (SMA) results from a mutation in the survival motor neuron 1 (SMN1) gene responsible for 90% of SMN protein production. Nusinersen, is the first treatment available for SMA I shown to improve motor function with limited data on respiratory function. The Great Ormond Street Respiratory (GSR) score was developed as an objective respiratory assessment tool for children with SMA I treated with Nusinersen. The score (1=stable/low support-26=poor reserve) takes into account SMA I subtypes, needs for physiotherapy and non-invasive ventilation. Aims: (1)To track the respiratory status of SMA I children over the course of Nusinersen treatment; (2)To compare the GSR scores of SMA I sub-types. Methods: SMA I patients were assessed using the GSR score at 3 time points: prior to first Nusinersen dose; 2 weeks post- 4th dose (end of loading doses); 2 weeks post-5th dose. Results: Sixteen SMA I children (7 males), underwent treatment with Nusinersen. The median age of diagnosis is 6 (IQR 3-10) months. Nusinersen was started at median of 11 (IQR 5.6-23.3) month-old. The median GSR [IQR] scores were: 9.5 [2.2-16.7] prior to 1st dose;16 ([.5-20.7] post- 4th dose; 17 [10-20.7] post- 5th dose. By 5th dose the SMA 1c children have lower scores than SMA 1b children (9 [IQR 6-16] vs 21 [IQR 18-22]; p=0.02). Discussion: Based on GSR scores, our SMA I cohort did not improve significantly in respiratory health in the early phase ofNusinersen therapy. By the 5th dose, the difference in respiratory status between Type Ib and Ic became apparent. Further longitudinal research is needed to chart the effect of Nusinsersen on motor and respiratory functions in SMA I patients.