Funded Studies
Study Rationale: Neuroinflammation plays a key role in the degeneration of dopamine-producing neurons and is critical in the pathogenesis of Parkinson’s disease (PD). Positron Emission Tomography (PET) is a noninvasive imaging technique that can be used to monitor biological processes, such as neuroinflammation, in real time. To make such observation possible, we propose to identify a stable compound that can detect the P2X7 receptor (P2X7R), a biomarker of neuroinflammation. Such a molecular tool could facilitate the early diagnosis of PD.
Hypothesis: By characterizing three different compounds, we predict that we can produce a novel P2X7R PET tracer that can be optimized to resist degradation and to accumulate in the brain — problems that plagued previously identified P2X7R PET tracer candidates.
Study Design: We will screen the selected molecules for properties that would make them ideal tracers for imaging studies: high affinity and selectivity for P2X7R, resistance to degradation and an ability to accumulate in the brain and to produce a high quality PET signal. The compounds will be further evaluated using brain tissue samples from people with PD to select the one that interacts most strongly P2X7R in the human brain. This molecule will be subsequently optimized as a P2X7R radiotracer for imaging of neuroinflammation.
Impact on Diagnosis/Treatment of Parkinson’s disease: Activation of P2X7R is linked to the early stages of immune-cell activation in the brain and the release of inflammatory chemicals. Therefore, a P2X7R PET tracer could help to better diagnose, monitor, and study neuroinflammation in PD.
Next Steps for Development: If successful, the next studies will confirm the ability of the PET tracer to detect changes in P2X7R in preclinical models of PD. Positive results in animal studies will ultimately pave the way for clinical trials in humans.