Objectives To determine whether plasma neurofilament light chain (pNfL) can be a reliable and minimally invasive biomarker for monitoring response in children with later-onset spinal muscular atrophy (SMA) undergoing nusinersen treatment.Methods Neurofilament light chain(NfL) levels were measured from plasma(pNfL) and cerebrospinal fluid (cNfL) of 40 children with later-onset SMA undergoing nusinersen treatment. A total of 480 CSF and plasma samples were taken during the first six doses of treatment from April 2021 to February 2023. Correlational analyses was used to determine the relationship of both pNfL versus cNfL and pNfL versus motor function.Results Both pNfL and cNfL levels exhibited significant reductions compared to baseline for the 40 children with SMA (pNfL: p<0.01; cNfL: p<0.01). indicating a strong correlation between pNfL and cNfL levels (r=0.73, p<0.01). A negative correlation was identified between the pNfL levels and the HFMSE scores ( r=-0.4, p<0.01).Conclusions This study indicates that pNfL can be used to monitor and evaluate the response of children with later-onset SMA undergoing nusinersen treatment.