Dr. Bakri Elsheikh and colleagues at The Ohio State University have published a paper in the Journal, Frontiers in Neurology, titled “Safety, Tolerability, and Effect of Nusinersen in Non-Ambulatory Adults with Spinal Muscular Atrophy.”

This project, funded by Cure SMA, investigated the safety, tolerability, and treatment effect of nusinersen treatment in non-ambulatory adults with SMA. Non-ambulatory individuals aged 18 years or older with genetically confirmed SMA were enrolled. Outcomes at 2-, 6-, 10-, and 14-months post-treatment were compared with baseline assessments.

Results from 12 women and 7 men (mean age: 39.7 ± 13.9; range: 21-64 years) were analyzed and demonstrated several important and relevant findings for the management of severely affected, non-ambulatory adults with SMA, a group that has been largely excluded from prior clinical trials. The study showed that nusinersen was well-tolerated, and 10-14 months of nusinersen treatment resulted in stability of outcome measures of ventilatory muscle function, muscle strength, and function. The primary outcome—forced vital capacity (FVC) —did not demonstrate improvement, but lack of decline may suggest a mild positive effect based on the expected decline noted in a recent large natural history study showing -1.32 to -0.67% predicted FVC reduction per year in patients with Types 2a and 3a SMA. Furthermore, these results provide evidence that some commonly used SMA outcome measures are not optimized for individuals severely impacted by SMA.

One of the most remarkable findings of the study were increases of compound muscle action potential (CMAP) and synchronous motor unit potential (SMUP) amplitudes. Adults undergoing treatment with nusinersen demonstrated enlargement of average motor unit size (amplitude) without change in motor unit number estimate (MUNE). This is particularly interesting because it differs from the response seen in children. The authors note that determining whether these differences were related to differences in technique or due to differences in biological response related to age (children vs. adults) deserves further attention in future studies.

Overall, this study supports the tolerability and suggests a positive impact of nusinersen in non-ambulatory adults with SMA. The authors conclude that future studies should focus on improvement of outcome measures for this population and understanding the impact of different routes of intrathecal delivery.