Study Rationale: Cells in the brain uses molecules such as dopamine, the neurotransmitter that is depleted in people with Parkinson’s disease (PD), to transmit signals from one to another. The secretion of these neurotransmitters is controlled, in part, by a protein called synaptic vesicular glycoprotein (SV2C). Studies have shown that SV2C is altered in PD. In this project, we propose to develop an imaging agent that permits to study the SV2C protein in the brain of living patients.
Hypothesis: We hypothesize that we can design a compound that binds to SV2C and, using advanced computerized models, we can then examine how these molecules interact. By adding a radioactive label to this compound, we hypothesize it can be used as an imaging agent for monitoring SV2C.
Study Design: Using advanced computerized models, we will identify and develop SV2C-binding molecules and use these compounds as probes in studies with imaging techniques such as positron emission tomography (PET) and autoradiography. We will perform these studies in rodents and non-human primates and in postmortem brain tissue from people with PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: SV2C could provide a specific biomarker for studying PD pathology. An imaging agent for SV2C can be a potential probe to assess the progression of the disease and the effects of treatments that can delay the degeneration of the nerve cells in PD.
Next Steps for Development: If successful, this project will contribute to the development of the first imaging agent for SV2C that can be applied to study people with PD.