# Serum creatinine to cystatin C ratio as a biomarker for monitoring motor-function in children with spinal muscular atrophy treated with nusinersen: a retrospective cohort study

## TL;DR

This study explores whether the ratio of creatinine to cystatin C in blood can help track motor function in children with spinal muscular atrophy undergoing treatment.

## Contribution

The study introduces the creatinine-to-cystatin C ratio as a potential biomarker for monitoring treatment response in pediatric SMA patients.

## Key findings

- CCR and creatinine levels were positively associated with motor function scores in SMA patients.
- CCR remained significant after adjusting for multiple factors, unlike creatinine.
- CCR levels increased significantly during treatment compared to baseline.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s12883-026-04657-3.