Promising Outcomes of Original Grant:
The goals of the original grant were to screen a library of compounds to identify leads for non-invasive imaging of PD pathology. We used cell culture models of alpha-synuclein aggregation and tissue sections from brain containing Lewy bodies. We identified several lead compounds that labeled Lewy bodies; some specifically over Alzheimer's plaques. The lead compounds have physical characteristics that suggest a good chance for brain entry.
Objectives for Supplemental Investigation:
With the identification of lead compounds, we will now characterize permeability across the blood-brain barrier. This will be accomplished with direct imaging of the vasculature of a pre-clinical model with multiphoton microscopy while injecting the compounds intravenously. This will allow us to watch in real time the effect on the pre-clinical model.
Importance of This Research for the Development of a New PD Therapy:
This work aims to identify a compound that enters brain and binds PD pathology specifically. The compound can then be radiolabeled and used as a molecular imaging probe using PET. This will ultimately allow quantitative imaging of PD pathology in humans to characterize the natural history of the disease and serve as an endpoint for therapeutic trials.