The alpha-synuclein protein is a key player in Parkinson’s disease (PD). Our ability to understand how this protein impacts the health of neurons in the brain is directly related to the tools we have at hand to study it. This study aims to validate an assay (test) designed to measure the amount of specifically modified versions of the protein in cerebrospinal fluid (baths the brain and spinal cord; CSF) that can be obtained from those with PD through a minimally invasive procedure.
This project is based on the hypothesis that modified versions of alpha-synuclein, phosphorylated alpha-synuclein, is directly relevant to PD, rather than the total amount of the protein found in biosamples.
The study will be carried out in two stages. The first stage will involve assay optimization and testing conditions in which outcomes will be robust and reproducible. In the second stage, we will analyze a large number of CSF samples from those with PD and explore if there are detectable differences between participants with Parkinson’s and control participants.
Impact on Diagnosis/Treatment of Parkinson’s disease:
When successfully completed, this assay will add a critical tool to our arsenal to measure and monitor phosphorylated alpha-synuclein in biosamples. There are major efforts underway to find therapeutic interventions that can change the course of the disease (slowing or stopping the progression) and the most advanced approaches involve targeting this protein. Thus, using this assay, we will be able to monitor if experimental therapies are effective for PD.
Next Steps for Development:
Upon completion of this work, the assay will be further developed toward a commercially available kit that can used in any laboratory or clinic where studies can be carried out by leading experts in the field.
Alpha-synuclein is a sticky protein that clumps in the brains of people with Parkinson's disease (PD). The main aim of this project was to test an assay (experimental setup) for its ability to measure a modified form of alpha-synuclein in biofluids of people with Parkinson's, for example, in the cerebrospinal fluid. This modified version (called pS129 alpha-synuclein) is thought to be associated with the disease process, but a robust and reliable way of measuring it is currently lacking. We have tested technical capabilities and reliability of the assay. Our findings suggested that the assay was well qualified for the intended purpose and should be tested further using a larger set of samples from people with PD and from healthy people.