Abstract
OBJECTIVE: To validate the clinical utility of creatinine-to-cystatin C ratio (CCR) as a biomarker for monitoring nusinersen treatment response in Chinese paediatric patients receiving nusinersen monotherapy. METHODS: In this retrospective, single-center study, 33 genetically confirmed 5q-SMA patients (≤ 18 years) treated with intrathecal nusinersen for ≥ 26 months (2020.2-2025.6) were enrolled. Motor function was serially evaluated using the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and Hammersmith Infant Neurological Exam Part 2 (HINE-2). Serum biomarkers, such as creatinine (Cr), creatine kinase (CK), and cystatin C, were measured at multiple time points. A linear mixed-effects model (adjusted for age, body mass index, SMA type, and treatment duration) was used to assess the biomarker-function associations. RESULTS: Ambulant patients and those with four SMN2 copies demonstrated elevated CCR and Cr levels compared to non-ambulant patients and those with three SMN2 copies at baseline. Serum CCR levels were significantly higher than the baseline at V4-V8 (10-26 months). Cr levels were significantly higher than the baseline at V8 (26 months), whereas CK and cystatin C levels remained unchanged. In the fully adjusted linear mixed-effects models, both CCR and Cr were positively associated with HFMSE and RULM scores. However, only CCR remained significant after adjustment. Cystatin C levels were inversely correlated with the HINE-2 scores. CONCLUSION: CCR is a promising biomarker in paediatric SMA patients receiving nusinersen monotherapy; however, its validity and generalizability require confirmation in larger, more diverse multicenter cohorts.