Sphingosine-1-Phosphate, Motor Severity, and Progression in Parkinson's Disease (MARK-PD)

Abstract

Background: Treatment with sphingosine-1-phosphate (S1P) agonists confers neuroprotective effects in animal models of Parkinson's disease (PD). Objectives: We assessed the association of serum S1P levels with motor and cognitive symptoms in patients with PD. Methods: S1P concentrations were analyzed with liquid chromatography–tandem mass spectrometry (LC–MS/MS) in serum of 196 PD patients and in 196 age- and sex-matched controls. Motor (Unified Parkinson's disease rating scale III [UPDRS III], Hoehn and Yahr) and cognitive (Montreal Cognitive Assessment [MoCA]) function were assessed at baseline. Follow-up data was available from 64 patients (median [interquartile range], 513 [381–677] days). Results: S1P levels were lower in PD patients compared with controls, that is 1.75 (1.38–2.07) and 1.90 (1.59–2.18) μmol/L, respectively (P = 0.001). In PD patients, lower S1P concentrations were associated with higher UPDRS III scores and Hoehn and Yahr stage. In the follow-up cohort, S1P concentrations below the median were associated with faster motor decline (hazard ratio: 4.78 [95% CI, 1.98, 11.50]), but not with cognitive worsening. Conclusions: Our observations reveal an association of S1P with PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.