Blood serum levels of neurofilament light chain (sNfL) reliably reflect cerebrospinal fluid neurofilament light chain values (cNfL) of patients with spinal muscular atrophy (SMA), according to a new study published in Annals of Clinical and Translational Neurology.

The levels of sNfL correlated with changes in motor function in SMA patients receiving treatment with nusinersen (Spinraza®). This occurred in patients with 2 copies of the SMN2 gene as well as 1 patient with more than 2 copies but only during the early stages of life, the authors said.

“Strong correlations between sNfL and cNfL together with motor function suggest that sNfL may be a suitable biomarker for disease activity in children with 2 SMN2 copies and those with >2 SMN2 copies within their initial stages during early childhood,” according to the authors.

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No correlation was seen between sNfL levels and changes in motor score in the other patients with >2 SMN2 genes. Nitz et al said this was most likely because there was not a significant improvement in motor scores seen in these patients during the study.

In SMA patients with 2 SMN2 copies, treatment doses of nusinersen were associated with decreases in sNfL levels and increases in scores from the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) test. Moderate to strong negative correlations using both Pearson and Spearman correlation coefficients were observed between CHOP INTEND scores and sNfL levels (Pearson, r =-.9, P =.005; Spearman, r =-.6, P =.134).

No correlation was observed in patients with >2 SMN2 genes between sNfL levels and the Hammersmith Functional Motor Scale Expanded (HFMSE) test that was used (Pearson, r =0.0, P =.920; Spearman, r =-.1, P =.744). One patient with >2 SMN2 copies was much younger than the other patients in this group and was therefore analyzed using the CHOP INTEND rather than HFMSE. This patient showed a strong inverse correlation between CHOP INTEND and sNfL levels (Pearson, r =–.9, P =.236; Spearman, r =–1.0, P =.333).

In addition to the data collected in 18 SMA patients (4 children with 2 copies of SMN2), data were also collected from 97 healthy participants between the ages of 2 months and 18 years. Data from this healthy cohort revealed that sNfL levels are significantly higher in infants through 4 years of age compared to children and adolescents between 5 and 18. No differences in sNfL levels were observed between sexes.

Patients with 2 copies of SMN2 had significantly higher sNfL levels before treatment initiation compared to patients with >2 copies. In contrast to median values for healthy control participants, patients with 2 copies had sNfL 50-fold higher levels while patients with >2 copies were 2-fold higher.


Nitz E, Smitka M, Schallner J, et al. Serum neurofilament light chain in pediatric spinal muscular atrophy patients and healthy children. Ann Clin Transl Neurol. 2021;(acn3.51449). doi:10.1002/acn3.51449