Researchers will develop and validate a new MRI imaging technique to visualize how neural degeneration actually occurs over time in a single neural circuit in Parkinson’s disease. Then they will use this MRI imaging technique to validate its potential for monitoring experimental gene therapies in Parkinson’s disease patients.
MRI imaging currently is not equipped to visualize neural circuits in the “nigro-striatal tract,” which degenerates in Parkinson’s disease, because the tract is located so deep in the brain. This tract is composed of cells located in substantia nigra, which produce the chemical messenger dopamine. The cells’ axons (communication cables) project into the brain’s striatum to communicate with cells there that control movement. In Parkinson’s disease, the dopamine-producing cells die, and the cells that control movement degenerate. Scientists rely on autopsy studies of the animal model to assess the effects of experimental therapies. This requires a lot of animals, sacrificed at various time points. Moreover, scientists cannot view this process as it occurs. These investigators will develop and validate an MRI imaging technique to visualize the degenerative process in real time. This requires testing in the animal model a number of MRI marker genes that may provide high resolution of specific brain circuits in the substantia nigra.
They will use a type of recombinant virus—called “adeno-associated viruses (rAAV)”—which target but do not harm these circuits. These viruses will serve as a vehicle for delivering four types of biological “contrast agents” that they hypothesize will enhance the ability of MRI imaging to show the neural circuits involved in Parkinson’s disease. The one that works best will be used with MRI imaging to visualize a single circuit over a period of time to see exactly how degeneration and cell death occurs in the circuit. Then they will use green fluorescent protein with this technique to label and monitor genes that potentially be gene therapies for Parkinson’s disease. Once the imaging technique itself is validated, this MRI imaging technology can be directly applied to assessing gene therapy in Parkinson’s disease patients.
Significance: Once this MRI imaging technique is validated in the Parkinson’s animal model, it will provide an entirely new way to assess experimental gene therapies in Parkinson’s disease patients.