Study Rationale:
The alpha-synuclein protein accumulates in structures called Lewy bodies in the brains of those with Parkinson's disease (PD). These protein clumps are considered to be one of the key hallmarks of PD. However, Parkinson's researchers have not yet obtained consistent clinical results for alpha-synuclein analysis at the diagnostic level. Accurate measures from biological samples can be obtained from extensive standardization of assays (tests) but also depend on the time of collection, storage, and handling of the sample during analysis. Standardization efforts will be beneficial for the field if they are conducted with fully-validated assays to help to obtain world-wide consensus. At present, standard operating procedures have not yet been described for the measurement of alpha-synuclein, which hampers its integration into routine clinical assessment. The present project will fill the gap in the field of alpha-synuclein analysis by performing experiments at the pre-analytical and analytical levels.
Hypothesis:
It is important to obtain experimental evidence of the potential impact of each step in the process of alpha-synuclein analysis, starting from the collection of the sample to analysis in the lab. Some of the variables that must be standardized include comparison of sample types, selection of tube types, definition of transport conditions, freezing and thawing temperatures of the samples, methods used to analyze the samples and quality control tools, which can be used to qualify the outcome of the assay. Our standardization project is essential for the future integration of alpha-synuclein analysis into clinical trial testing and will take into account gaps that were identified by the "Alpha-synuclein Consortia." The project outcome will provide solutions for existing gaps and make a bridge between research recommendations and official guidance for alpha-synuclein analysis. The Michael J. Fox Foundation will have access to all data sets to publish recommendations to the field for the collection, storage and analysis of alpha-synuclein samples.
ADx NeuroSciences (ADx) has in-house experience to develop robust assays, harmonize results between studies and technologies and make recommendations for each step in the process. Although the road from concept to approved assays is long, ADx has tools and know-how to bring alpha-synuclein measurements closer to regulatory approval. ADx will also work closely with expert centers and key opinion leaders in the field.
Study Design:
Our project will provide standard operating procedures for alpha-synuclein measurements by performing experiments with fully validated alpha-synuclein assays (commercially available in Q2 2017). The experimental protocols will combine several parameters and results will be analyzed by statistical experts.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The availability of standardized operating procedures for sample collection and analysis, together with the availability of a validated second generation assay of alpha-synuclein, will allow faster integration of this biomarker test into large-scale clinical trials and studies. In addition, it will allow the field to use alpha-synuclein in the diagnosis and management of PD.
Next Steps for Development:
The ultimate goal of this project is to include the measurement of alpha-synuclein into the diagnostic guidelines for Parkinson's.