Abstract
Spinal muscular atrophy (SMA) is a genetic neurodegenerative disorder leading to immobilization and premature death. Currently, three alternative therapeutic options are available. Therefore, biomarkers that might reflect or predict the clinical course of the individual patient with treatment are of great potential use. Currently, the antisense oligonucleotide nusinersen is the prevalent and longest validated therapy for SMA. We analysed CSF candidate biomarkers for degenerative CNS processes (namely phosphorylated heavy chain (pNf-H), light-chain neurofilaments (NfL), total tau protein (T-Tau), neurogranin, β-secretase BACE-1 and alpha-synuclein) in 193 CSF samples of 44 paediatric SMA types 1, 2 and 3 patients before and under nusinersen treatment and related them to standardized clinical outcome scores in a single-centre pilot study. pNf-H and NfL correlated with disease severity and activity, emphasizing their relevance as marker of neuronal loss and clinical outcome. T-Tau was significantly correlated with motor function scores in SMA type 1 making it an interesting marker for treatment response. Additionally, baseline T-Tau levels were elevated in most SMA patients possibly reflecting the extension of neuronal degeneration in paediatric-onset SMA. Further investigations of these CSF proteins might be beneficial for paediatric SMA subtypes and treatment modalities as an indicator for clinical outcome and should be analysed in larger cohorts.