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Research Article: Longitudinal motor function and biomarker correlates in treated adult spinal muscular atrophy: a single-center cohort study

Date Published: 2026-06-11

Abstract:
Long-term clinical trajectories and accessible biomarkers in adult spinal muscular atrophy (SMA) remain insufficiently characterized under real-world treatment conditions. We conducted a single-center longitudinal study to evaluate motor function, genotype–phenotype relationships, and clinically accessible biomarkers in treated adults with SMA. Twenty-three Japanese adults with genetically confirmed 5q-SMA treated with nusinersen or risdiplam (2018–2025) underwent repeated assessments of Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), and laboratory, physiological, and electrophysiological measures. Associations were explored using correlation analyses, linear mixed-effects models, and exploratory machine-learning approaches. Higher SMN2 copy number was associated with later onset and milder severity. Hybrid SMN alleles showed heterogeneous patterns depending on copy-number context. Longitudinally (mean follow-up 57?months), motor scores often improved or stabilized during the first year after treatment initiation, followed by plateau or gradual decline in some patients. In mixed-effects models, vital capacity (%VC) was independently associated with RULM, while other biomarkers showed consistent associations with motor scores. Exploratory machine-learning suggested that ulnar compound muscle action potential (CMAP) amplitude and creatine kinase (CK) contributed to model predictions, although baseline features did not reliably predict short-term motor changes. In treated adults with SMA, simple clinical measures such as %VC, CK, ulnar CMAP amplitude are associated with motor status and may support routine monitoring, while prediction of treatment responsiveness remains challenging.

Introduction:
Long-term clinical trajectories and accessible biomarkers in adult spinal muscular atrophy (SMA) remain insufficiently characterized under real-world treatment conditions. We conducted a single-center longitudinal study to evaluate motor function, genotype–phenotype relationships, and clinically accessible biomarkers in treated adults with SMA.

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