Lactate Lowering and Neuroprotection

There are currently no treatments for the neurodegeneration that occurs following a stroke or head trauma. Recent breakthroughs in understanding of the mechanisms by which nervous tissue degenerates have made it possible to design therapeutic drug strategies to prevent the process. We will develop rational drug treatments for stroke and head trauma, i. e. neuroprotective drugs. The current neuroprotective drug candidates are proving not to be clinically useful due to their substantial side effects. This proposal will characterize a drug that lowers post-ischemic lactic acid levels and in so doing inhibits tissue damage. The lactate lowering agent will be tested in several animal models of stroke, and its efficacy compared to another putative neuroprotective drug. The Phase I goals are to establish the efficacy of our lead agent with special consideration given to documenting its therapeutic value when given following reperfusion. In Phase II a medicinal chemistry effort will seek to develop more potent agents which act via the same mechanism. A structure-activity relationship will be generated for these agents. Extensive animal testing will evaluate these optimized agents.