Imaging is a powerful tool that can be used to visualize the structure and function of the brain in living subjects. In this study, we aim to develop a new brain imaging chemical (agent) for visualization of alpha-synuclein, a sticky protein that clumps in the brains of people with Parkinson's disease (PD). Such an agent would be used in positron emission tomography (PET) imaging to diagnose Parkinson's early and track disease progression, as well as monitor the efficacy of therapies that reduce alpha-synuclein clumping. We identified several promising compounds and will develop next-generation compounds for clinical use based on these as alpha-synuclein imaging agents.
We aim to develop novel alpha-synuclein imaging agents that satisfy several key criteria. First, the agents must have the ability to stick to alpha-synuclein clumps specifically and not to other proteins; they must stick to alpha-synuclein that is just starting to clump. Importantly, they must travel to the brain easily and leave the brain quickly, remaining there only for the duration of the imaging procedure.
We have already identified compounds with suitable properties including the ability to stick to alpha-synuclein. In this study, we will produce new compounds based on the most promising compounds identified in the past. We will then test whether the new compounds satisfy our key criteria, such as the ability to stick to alpha-synuclein selectively and to travel in and out of the brain. We will use samples of brain tissue donated by people after death as well as in vitro experimental setups to accomplish these goals.
Impact on Diagnosis/Treatment of Parkinson's Disease:
An imaging agent for alpha-synuclein would improve the accuracy of early diagnosis of Parkinson's disease and similar disorders called synucleopathies. It will also play a major role in clinical trials of disease progression as a biomarker (an objective measure of disease).
Next Steps for Development:
If successful, this study would produce alpha-synuclein imaging compounds designed to be used as clinical tools. Next steps toward their clinical use would involve modification of the compounds and their subsequent evaluation in pre-clinical models, and, eventually, in clinical trials.