Is cerebrospinal fluid amyloid‐β42 a promising biomarker of response to nusinersen in adult spinal muscular atrophy patients?

INTRODUCTION: Nusinersen was approved as the first treatment for all types of spinal muscular atrophy (SMA), including adults with SMA types 2 and 3. Robust biomarkers of treatment response in SMA adults are lacking. Our aim was to examine cerebrospinal fluid (CSF) amyloid‐β40 (Aβ40) and amyloid‐β42 (Aβ42) peptides as biomarkers of treatment response. METHODS: Eight patients with SMA types 2 and 3 were recruited consecutively in a single‐center study. CSF was sampled at baseline, after a loading dose, and after three maintenance doses. Levels of Aβ42 and Aβ40 were evaluated for each CSF sampling. Wilcoxon matched‐pairs signed‐rank test was used to detect longitudinal changes. RESULTS: CSF levels of Aβ42 increased from baseline to day 420 (95% confidence interval, P = .018), with a significant increase at days 180 and 420 compared with days 0 and 300, respectively (95% confidence interval, P = .012 and P = .018). DISCUSSION: The maintenance and promotion of wellness of residual motor neurons mediated by the restored level of SMN protein due to nusinersen could result in an increased level of amyloid peptides.