Study Rationale: In Parkinson’s disease (PD), a protein called alpha-synuclein builds up inside of brain cells. Research suggests that this protein accumulation damages the cells and eventually leads to the symptoms of PD. The ability to see alpha-synuclein on a brain scan would help us understand how the protein builds up, so we can develop effective new drugs for treating PD. Alpha-synuclein can be detected by a noninvasive imaging procedure called positron emission tomography (PET), but the technique requires a special tracer to highlight the protein’s location.
Hypothesis: We hypothesize that we can develop an alpha-synuclein PET tracer that will allow us to noninvasively measure alpha-synuclein in the human brain.
Study Design: Using an extensive series of experiments designed to identify and optimize the properties of potential PET tracers, we will develop a tracer with excellent selectivity for alpha-synuclein, low binding to normal brain tissue and a good pharmacokinetic profile. We will also use an automated, miniaturized binding assay in brain tissue from people with PD to assess alpha-synuclein affinity.
Impact on Diagnosis/Treatment of Parkinson’s disease: An alpha-synuclein PET tracer could be used to evaluate the concentration of alpha-synuclein in the brain at diagnosis and during PD progression, help determine which individuals should be treated with which drugs and evaluate new treatments in clinical trials.
Next Steps for Development: After identifying an alpha-synuclein PET tracer, we will test the tracer in people with PD. We will perform studies to confirm a higher PET signal in brain regions known to be rich in alpha-synuclein. Further efforts will focus on making the PET tracer broadly available for use in clinical trials.