Study Rationale: Alpha-synuclein aggregates are considered to be an excellent biomarker for the diagnosis of Parkinson’s disease (PD). The challenge is to optimize the tests currently used to detect these aggregates or “seeds” (called Seed Amplification Assays, SAA) so they can be used in the clinic. In this project, we will accelerate our current method to provide more rapid results for patients seeking a PD diagnosis. In addition, we will explore methods for estimating the quantity of these alpha-synuclein seeds in clinical samples, information that could correlate with disease status and the future progression of PD.
Hypothesis: We hypothesize that we can accelerate our SAA approach without decreasing the diagnostic accuracy of the method. In addition, we hypothesize that individuals with very early signs of PD (those who are prodromal) will harbor smaller quantities of apha-synuclein aggregates.
Study Design: We will enhance the speed of our method by making changes to the workflow and to the assay itself. To assess our ability to accurately determine the quantity of alpha-synuclein seeds in clinical samples, we will perform multiple measurements on a series of increasingly diluted samples. Finally, we will use our optimized method to examine samples from individuals who are prodromal or have been diagnosed with PD and to determine whether these samples differ in the amount of alpha-synuclein seeds they contain.
Impact on Diagnosis/Treatment of Parkinson’s disease: A quick and reliable diagnostic test would not only help patients seeking a definitive diagnosis, but it will also further our understanding of the disease. This method could also help pharmaceutical companies to determine which drugs are most effective at reducing alpha-synuclein aggregates in people with PD.
Next Steps for Development: If successful, this project will generate a test that can be used by clinics and pharmaceutical companies to diagnose and evaluate drugs in development for PD. This method could also be used to screen compounds for their ability to reduce alpha-synuclein aggregates early in the drug development process.