Study Rationale:
The goal of this study is to develop an imaging tool (a radiotracer) that could be used to show the protein alpha-synuclein in the brains of living people with a brain scan call a positron emission tomography (PET) scan. Alpha-synuclein clumps in the cells of people with Parkinson's and other brain diseases called synucleinopathies, which include Lewy body dementia and multiple system atrophy. This imaging tracer could be used to diagnose these diseases and to evaluate therapeutic strategies aimed at preventing or delaying alpha-synuclein aggregation.
Hypothesis:
This study seeks to identify small molecules with a high affinity for alpha-synuclein and low affinity for other proteins -- amyloid-beta and tau -- that are associated with other brain diseases such as Alzheimer's.
Study Design:
This project will utilize a novel ultrahigh-throughput method to identify lead compounds having a high affinity for alpha-synuclein versus amyloid-beta and tau. This method takes advantage of our recent studies identifying multiple binding sites for small molecules in alpha-synuclein, and the availability of digital methods that enable rapid screening of large chemical libraries to identify lead compounds for radiotracer development.
Impact on Diagnosis/Treatment of Parkinson's Disease:
If successful, this project could lead to the development of a novel imaging technique to study the role of alpha-synuclein in Parkinson's and other synucleinopathies. It will also provide a valuable method for measuring the therapeutic efficacy of drugs designed to treat these diseases.
Next Steps for Development:
The next steps in this project will be the performance of toxicity and dosing studies to enable first-in-human studies of a PET radiotracer.