Development of Lewy Bodies MRI Imaging Agents for the Early Diagnosis of Parkinson's Disease and Related Disorders

Promising Outcomes of Original Grant:

Parkinson’s disease and related conditions are the most common movement disorders. Pathological studies reveal abundant protein deposits in the affected neurons, mainly formed by a protein named alpha-synuclein. The main objective of our original funded grant was to design a novel agent that binds specifically to alpha-synuclein aggregates. We were able to design smart compounds that bind specifically to alpha-synuclein aggregates formed in vitro or in cell models of Parkinson’s disease. These smart compounds are labeled with an MRI-detectable contrast agent. We found our compounds cross the blood-brain barrier after being injected intravenously into normal rodent pre-clinical models of PD.

Objectives for Supplemental Investigation:

In this project we are planning to:
1. Investigate the pharmacokinetics, bioavailability and toxicity of our compounds in normal mice.
2. Study the effects of the smart compounds in young and aged, normal and PD transgenic pre-clinical model brains using MRI.

Importance of This Research for the Development of a New PD Therapy:

The goal of our study is to provide a new tool for an early diagnosis of Parkinson’s disease, by imaging specifically alpha-synuclein aggregates either as pre-Lewy bodies or mature Lewy bodies in the brain.