This grant builds upon the research from a prior grant: Development of a Radiolabeled Tracer for Detecting Insoluble Protein Aggregates in Parkinson’s Disease
Study Rationale: Alpha-synuclein is a key protein involved in the pathology of Parkinson’s disease (PD). We recently confirmed that two compounds developed under the MJFF Alpha-synuclein Imaging Consortium show a higher affinity for alpha-synuclein and a better ability to discriminate between alpha-synuclein and amyloid-beta, a protein involved in Alzheimer’s disease, than originally thought. The goal of this supplement is to further characterize the radiolabeled version of these compounds, BF3620 and RO186368, in brain slices and in the brains of nonhuman primates.
Hypothesis: We hypothesize that these tracers will have a high brain uptake and a rapid rate of washout with a peak signal at 60 minutes, and we expect a version of the compounds labeled with tritium will bind to alpha-synuclein present in postmortem brain slices of the PD brain.
Study Design: We will conduct imaging studies with the carbon-11 labeled compounds to measure the uptake and rate of washout from the brains of nonhuman primates. We will also perform autoradiography studies in sections taken from the brains of people with PD and with multiple system atrophy (MSA) using the tritium-labeled versions of BF3620 and RO186368. These studies will indicate whether the compounds bind to alpha-synuclein present in the PD or MSA brain.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this project could lead to the development of a radiotracer for PET imaging studies to clinically characterize people with PD and MSA.
Next Steps for Development: If the compound(s) meet the milestones we have set out, we will recommend that one or both compounds be advanced to first-in-human imaging studies.