Neurofilaments in cerebrospinal fluid and/or serum as a possible biomarker of pediatric spinal muscular atrophy

Background Spinal muscular atrophy (SMA) is a severe, genetically determined neuromuscular disorder characterised by progressive muscle weakness resulting from motor neuron degeneration. Although therapies such as nusinersen have altered disease trajectories, objective biomarkers for treatment monitoring remain lacking. Neurofilament proteins, particularly phosphorylated neurofilament heavy chain (pNFH), are promising candidates for this role. Objectives To evaluate pNFH levels in cerebrospinal fluid (CSF) and serum as potential biomarkers for monitoring treatment response to nusinersen in paediatric patients with SMA. Methods This two-center observational study involved 56 SMA patients (types I–III) treated with nusinersen and 30 age-matched controls. pNFH concentrations in CSF and serum were measured at predefined intervals using ELISA kits. Motor function was assessed with CHOP INTEND, HFMSE, or MFM scales at baseline and after 3, 6, and 12 months. Mixed linear regression modeling evaluated changes in neurofilament levels and motor function. Results Baseline pNFH levels in both CSF and serum were significantly higher in SMA patients compared to controls. Following nusinersen therapy, pNFH levels decreased significantly in both compartments, especially in the first 6 months. Younger patients had higher initial serum pNFH levels. A significant correlation was found between CSF and serum pNFH concentration. An association between pNFH levels and motor scores was observed. Conclusions pNFH levels in CSF and serum show potential as objective biomarkers for monitoring the initial treatment response in paediatric SMA. Longitudinal changes are more informative than single measurements. Further validation in larger cohorts and using more sensitive methods is warranted.