Study Rationale:
Alpha-synuclein is a protein that aggregates in several brain diseases, including Parkinson’s, dementia with Lewy bodies and multiple system atrophy. There is no established method for measuring alpha-synuclein aggregates in living humans. This project will use our collection of aggregated protein-targeting small molecules and our experience in developing PET imaging agents to enable a new tool to image alpha-synuclein.
Hypothesis:
This project aims to identify a small molecule to be used in PET imaging of alpha-synuclein.
Study Design:
We will evaluate our alpha-synuclein-binding collection of compounds in numerous laboratory tests to determine feasibility of these compounds as PET imaging agents. First compounds will be ranked according to their physical properties (e.g., solubility) and then be radiolabeled for tests in binding to diseased tissue. Next compounds with desirable profiles will be tested for safety and efficacy in pre-clinical models.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Our alpha-synuclein PET imaging tracer would enable more accurate diagnose of various brain diseases related to the alpha-synuclein protein. It would also help physicians classify patients with different disease progression stages more accurately and allow early efficacy evaluation of new therapies.
Next Steps for Development:
The compound with the best results will be selected for further evaluations of feasibility for mass-production of drug product. Then, it will be synthesized at hospitals as the radioactive tracer for clinical trials.