To describe CSF levels of neurofilament-light chain (NfL), glial fibrillary acidic protein (GFAP) and Tau in a cohort of patients with a wide spectrum of disease severity and age at time of treatment initiation, both at baseline and following treatment with nusinersen.

Availability of new therapies for spinal muscular atrophy (SMA) calls for sensitive biomarkers to track disease and treatment response. 

Pre-treatment NfL levels were higher in children with type 1 versus type 2 (p=0.020) and 3 (p<0.0001), and were negatively correlated with baseline CHOP-INTEND (p=0.042) and HFMSE scores (p=0.0011). GFAP levels were higher in patients than controls (p<0.0001), and in type 1 than type 3 (p=0.0073). Motor function improved in children with all SMA types following treatment (type 1 and 2 p<0.0001, type 3 p=0.0056), particularly in younger children. NfL levels decreased rapidly in all SMA types upon treatment initiation (p<0.0001), more steeply in type 1 vs type 3 (p<0.0001), and in younger children (p=0.0029). Greater decreases were associated with more pronounced clinical responses in type 1 (p=0.020). GFAP levels modestly decreased in type 1 (p=0.026) while Tau levels decreased in all SMA types (p<0.0001). 

We observed increased levels of neuronal and astrocytic markers in SMA patients, associated with disease severity and decreasing following treatment initiation, suggesting a potential for NfL, GFAP and Tau as biomarkers of SMA severity and treatment response.