This grant builds upon the research from a prior grant: Developing a Reliable Clinical Test for pS129 Alpha-synuclein
Study Rationale:
In Parkinson's, there remains an unmet need for biomarkers to track disease progression and efficacy of potential therapies. This team of investigators is focused on fluid-based measurement of the abnormal protein pS129 alpha-synuclein, which can serve as an indicator of disease progression. With previous funding from The Michael J. Fox Foundation, the team identified several factors that negatively impacted its ability to measure pS129 alpha-synuclein protein correctly in cerebrospinal fluid (CSF), which it plans to address in this study.
Hypothesis:
The objective is to design more accurate assay and sample preparation protocols for the measurement of alpha-synuclein in CSF.
Study Design:
The team plans to carry out experiments in three parts. First, they will test ways to improve detection of alpha-synuclein by reducing the steps needed to process the sample and reduce losses in these steps. Next, they will uncover how antibodies directed to a specific subset of alpha-synuclein is affected by various modifications and develop a way to account for these modifications while determining the quantity of alpha-synuclein. Finally, they will incorporate synthetically generated proteins as calibrators in the assays in which they find modifications either individually or in combination to compare between studies.
Impact on Diagnosis/Treatment of Parkinson’s disease:
To develop better treatments for Parkinson’s, researchers need tools to assess the effect of potential treatments. Robust reliable and reproducible assays to quantify targets that we know are related to the disease are therefore critically important.
Next Steps for Development:
This study will enable the team to advance a robust assay platform toward the assessment of valuable clinical cohorts.