J Clin Neurol. 2026 May;22(3):327-337. doi: 10.3988/jcn.2025.0556.
ABSTRACT
BACKGROUND AND PURPOSE: Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked neuromuscular disorder characterized by slowly progressive motor decline. However, there is no specific fluid marker that reflects the severity or progression of the disease. Therefore, identifying measurable markers that reflect disease progression remains a major unmet need in SBMA management.
METHODS: Plasma samples from 21 Korean patients with SBMA were collected at baseline and after 3 years. Untargeted and targeted metabolomics profiling was performed, and plasma sphingosine-1-phosphate (S1P) was the final candidate biomarker. S1P was then quantified using liquid chromatography-mass spectrometry. Associations between longitudinal S1P changes and clinical parameters, including the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), serum creatine kinase (CK), 6-minute walk test (6MWT), and forced vital capacity (FVC), were examined.
RESULTS: Plasma S1P levels significantly declined in the fast progression group over 3 years, while remaining relatively stable in the slow progression group. Longitudinal changes in plasma S1P showed weak-to-moderate positive trends with clinical measurements, including ALSFRS-R, FVC, and 6MWT, and a negative trend with serum CK at follow-up.
CONCLUSIONS: Plasma S1P represents a promising quantitative biomarker for monitoring SBMA progression. Validation in larger cohorts and mechanistic studies of S1P regulation are warranted to establish its role in clinical management.
PMID:42108848 | DOI:10.3988/jcn.2025.0556