Objective/Rationale:
Clinical trials with a number of agents suggest that the ability of compounds to move through the interstitial spaces of the brain is a critical factor for their effectiveness. Our goal is to develop new methods for measuring movement of agents in areas affected by Parkinson’s disease, and to use these methods to measure how drugs move in the brain in different conditions.
Project Description:
Our goal is to develop new techniques for imaging the movement of molecules in the brains of living animals, and to use these new techniques to determine how molecules relevant for treatment of Parkinson’s disease move in the brain. First, we will use high resolution optical imaging techniques that provide quantitative measurements of agent movement and detailed images of local neuroanatomy. Therefore, this study will be the first to correlate molecular movement with the local brain architecture. Second, we will use novel deep-brain techniques that permit real-time imaging of cellular events that regulate local movement, such as cellular binding/uptake and entry into microvasculature.
Relevance to Diagnosis/Treatment of Parkinson’s Disease: Studies over the past 15 years have revealed mechanisms of movement for some agents in the brain, but a general framework for predicting movement of molecules in the brain is lacking. This proposed work represents a significant advance over this prior work. By combining new, real-time techniques with conventional analysis of agent movement, we will develop a comprehensive view of the barriers to molecular movement for agents of interest in the striatum. We anticipate that our results will provide the basis for the design of new approaches for drug delivery in PD.
Anticipated Outcome:
This collaborative research project will result in a quantitative understanding of the barriers to movement of agents in regions of the brain affected by Parkinson’s disease. In addition, as the project moves forward, we will test the effects of experimental approaches that are designed to overcome the barriers to movement. This will be accomplished by measuring the movement of agents after selected chemical modification or nanoencapsulation.
Progress Report
The novel microscopy technique developed in the study (combining gradient index lens with fluorescence recovery after photobleaching) required extensive optimization of the equipment and the technique by the research team. The group has demonstrated feasibility of the technique in solution and is currently testing feasibility in vivo.