This grant builds upon the research from a prior grant: Use of NR2D-selective NMDA Receptor Modulators in the Treatment of PD
Promising Outcomes of Original Grant:
The goal of the original grant was to identify new chemical compounds that block specific types of receptors for the neurotransmitter glutamate and test whether these alter neuronal function in a brain region (subthalamic nucleus) involved in the generation of parkinsonism. We have discovered several new classes of subunit-selective glutamate antagonists that block the receptors that contain the GluN2D subunit in subthalamic nuclei.
Objectives for Supplemental Investigation:
We now are testing beneficial effects of the best compounds (most potent, most active, safest) in a pre-clinical model of parkinsonism. Electrical recordings of nerve cells in this region will assess whether the experimental treatment improves nerve cell activity, and behavioral assessment will determine whether movement is altered. The objectives are two-fold. First, we will characterize the properties of the new experimental molecules. Second, they will be administered to models with lesions of dopaminergic neurons that create movement disturbances similar to those found in Parkinson’s disease.
Importance of This Research for the Development of a New PD Therapy:
Completion of these experiments will provide the first assessment of subunit-selective NMDA glutamate receptor antagonists in pre-clinical models of Parkinson’s disease. This class of drugs could develop to clinical testing, if successful.