Prospective, multicenter, longitudinal observational study of adults with SMA Type II/III who are initiating nusinersen. We report the raw mean ± SD [N] change from baseline over time and p-value of the model-estimated means from a repeated measures linear mixed model.

As of September 2020, 40 patients (18 female; 12 ambulatory; 3, 18, and 19 with 2, 3, and ≥4 SMN2 copies, respectively) with mean (SD) age 37.6 (11.9) years are enrolled. Available assessments at day 15, day 60, and month 6 showed early and modest improvements in the Revised Upper Limb Module (1.3 ± 1.8 [27]; 1.0 ± 2.0 [27]; 1.0 ± 1.9 [18]; all p≤0.005), Revised Hammersmith Scale (0.9 ± 1.7 [33]; 1.0 ± 2.6 [34]; 1.2 ± 3.6 [22]; all p≤0.04), and Maximum Expiratory Pressure (7.5cm H₂0 ± 16.9 [30]; 6.8 ± 16.9 [27]; 9.7 ± 20.6 [15]; all p<0.05). Improvements also occurred at day 60 and month 6 in SMA-Health Index, as illustrated by lower scores over time, (-6.7 ± 17.7 [37]; -5.3 ± 20.6 [21]; all p<0.05) and at 6 months in %Predicted Forced Vital Capacity (3.7 ± 6.9 [15], p=0.006). There was stability through month 6 in the Maximum Inspiratory Pressure (-6.2cm H₂0 ± 14.9 [15], p=0.15) and, in the few ambulatory subjects, in the six-minute walk distance (-3.8m ± 47.8 [5], p=0.69). Six serious adverse events occurred, five were unlikely or not related, and one was possibly related to nusinersen.

Nusinersen is well tolerated in adults. We measured modest improvements in strength, function, and disease burden soon after treatment initiation that persisted through 6 months. Enrollment, data collection, and serial assessments over 30 months are ongoing.