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.