Session Information
Date: Thursday, June 23, 2016
Session Title: Clinical trials and therapy in movement disorders
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: The Systemic Synuclein Sampling Study (S4) is designed to characterize the distribution of alpha-synuclein (α-syn) pathology in multiple tissues and biofluids in Parkinson’s disease (PD) subjects and healthy controls (HC). A primary objective is evaluation of α-syn species as potential surrogate markers for patient selection/enrichment and disease staging to inform future clinical trials.
Background: Aberrant α-syn expression and misfolding play key roles in the pathogenesis of PD. Development of biofluid and/or peripheral tissue biomarkers for PD diagnosis and progression monitoring are critical for the advancement of therapeutics, and α-syn is a lead candidate marker. α-Syn pathology has been observed in peripheral autonomic nervous system and differences in α-syn levels in biofluids have been observed in PD compared with HC. Studies thus far have utilized small sample sizes evaluating single biofluid/tissue types with varied methodologies for collection, processing and analysis. S4 design evaluates α-syn species in multiple tissues and biofluids within the same subject at a single time point.
Methods: This is a multi-center, cross-sectional, observational study to evaluate α-syn pathology in multiple tissues and biofluids in individual subjects with PD and HC at a single time point. The S4 study plans to enroll 60 PD subjects (20 early drug naïve, 20 moderate on dopamine replacement without motor fluctuations, 20 advanced with motor fluctuations) and 20 HCs. Subjects will be characterized using clinical evaluations (MDS-UPDRS, MOCA, UPSIT) and dopamine transporter imaging. Standardized collection and processing of biofluids and tissue biopsies will enable centralized assessment of samples collected across sites. Whole blood, serum, plasma, saliva and CSF will be obtained and α-syn (total, phosphorylated, oligomeric and other α-syn species) levels will be quantitatively analyzed using validated assays. Tissue biopsies obtained from skin, sigmoid colon submucosa and submandibular gland for immunohistochemical analysis using a semi-quantitative analysis.
Conclusions: The S4 study design offers the possibility for characterizing intrasubject α-syn pathology in tissues and biofluids across the spectrum of disease severity and identifying the optimal matrix for measuring biomarkers in the drug development process.
To cite this abstract in AMA style:
D. Jennings, C. Coffey, T. Beach, T. Foroud, C.H. Adler, B. Mollenhauer, J. Seibyl, D. Ecklund, S. Lasch, V. Arnedo, C. Kopil. The systemic synuclein sampling study (S4) [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/the-systemic-synuclein-sampling-study-s4/. Accessed May 12, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-systemic-synuclein-sampling-study-s4/