Alpha-Synuclein Assay Standardization LEAPS (linked-efforts to accelerate Parkinson’s solutions)

Partners

Jing Zhang, MD, PhD, University of Washington, Seattle, Washington, United States

Omar El-Agnaf, PhD, Hamad Bin Khalifa University, Doha, Qatar,

Peggy Taylor, ScD, BioLegend, Inc., Massachusetts, United States

Brit Mollenhauer, MD, University Medical Center, Goettingen, Germany

Robert Umek, PhD, Meso Scale Discovery, Maryland, United States

Henrik Zetterberg, MD, PhD, University of Gothenburg, Mölndal, Sweden

Hilal A. Lashuel, PhD, EPFL-Lausanne, Switzerland, in collaboration with the EPFL Proteomic Core Facility, EPFL-Lausanne (Dr. Adrien Schmid and Dr. Marc Moniatte)

 

Study Rationale

The presence of alpha-synuclein protein in biofluids such as blood, cerebrospinal fluid and saliva has been reported by multiple scientists using a variety of analytical techniques. Results suggest that alpha-synuclein levels may be different in Parkinson’s disease (PD) patients compared to controls, at least in the cerebrospinal fluid. Thus alpha-synuclein assessment in accessible body fluids may serve as a biomarker for PD. However, in order to qualify human alpha-synuclein protein in body fluids as a biomarker, it is imperative to establish a standardized assay (laboratory test) that has undergone rigorous validation. The assays utilized to date to detect various forms of alpha-synuclein have been developed primarily for research use in individual laboratories and may not be suitable for controlled clinical trials. The Michael J. Fox Foundation (MJFF) is intent on accelerating the adoption and incorporation of a validated alpha-synuclein assay into observational and interventional clinical trials as well as in preclinical studies. Read more…

Program Goal

MJFF has chosen to support a collaborative consortium comprising all-star laboratories from academia and industry that have the necessary experience and expertise to assess multiple alpha-synuclein research assays for consistency of performance through sharing of protocols, reagents, samples and data.

Study Design

This consortium consists of several teams that are each headed up by the investigator who developed the assay to be tested. Each team consists of multiple laboratories that will compare the performance of that assay in the same samples, thus allowing for a “round robin”-type comparison of how the assay performs in different “hands” and under different conditions. Each assay will assess alpha-synuclein levels in cerebrospinal fluid, whole blood and saliva samples. Another important goal of this project is a thorough examination of various factors that might influence assay performance and explain assay variability, such as how the samples are handled, stored and processed.

Impact on Diagnosis/Treatment of Parkinson’s Disease 

A thorough investigation of the currently available alpha-synuclein assays and the factors that affect their variability should enable the development of a standardized protocol, which can be utilized in clinical validation and trials. Thus, these types of assays, once thoroughly validated, could not only be used to identify patients who may go on to develop PD or determine PD progression, but could also represent mechanisms to determine whether a drug is “working” in a clinical trial. To date there is no currently available fully validated biomarker assay to establish drug efficacy.