Study Rationale: Seed Amplification Assays (SAAs) can detect minute amounts of alpha-synuclein deposits (called seeds) in cerebrospinal fluid (CSF) and other biofluids of Parkinson’s patients. They can thus enable a reliable diagnosis even at very early disease stages. In order to monitor disease progression and treatment effects, these assays must be improved so that they can quantify the amount of seeds in patient samples. We have created a new technology platform called SeRAS® (Seed Replication, Analysis and Subtyping) that allows us to precisely control the physical seed amplification reaction parameters. In this study, we propose to use this technology to quantify synuclein seeds in CSF of Parkinson’s patients.
Hypothesis: We hypothesize that a process called secondary nucleation is a major obstacle for quantitative SAAs and that the superior SeRAS assay control and analysis will allow to achieve reaction conditions that enable quantification.
Study Design: We will first identify appropriate SeRAS reaction parameters and adjust the biochemical composition of the assay to faithfully detect synuclein standard seeds. In a second step, we will further adjust the reaction parameters to quantify synuclein seeds in the CSF of patients with Parkinson’s and other, synuclein-related diseases such as Lewy body dementia or MSA. Finally, we will validate our new synuclein SeRAS assay with a set of blinded CSF samples.
Impact on Diagnosis/Treatment of Parkinson’s disease: A quantitative synuclein SAA will help to monitor the treatment success of new drugs against Parkinson’s disease, and will provide information on disease progression. In addition, we hope to be able to gather new information that will allow to differentiate Parkinson’s disease from other synuclein-related disorders even at early disease stages.
Next Steps for Development: We will next adjust our SeRAS assay to more easily accessible materials such as blood or skin samples. In addition, we will apply our assay to a larger set of patient samples in order to better validate its performance.