A Novel Neuroprotectant to Reduce Ischemic Injury

Massachusetts General Hospital, Boston MA

Investigators

Abstract

The goal is to develop novel therapeutics effective in stroke. This will be achieved by providing evidence for in vivo activity of our lead compound in a rat stroke model as well as supportive pharmacokinetic and pharmacodynamic (PK/PD) assay data. We have identified potent and highly selective inhibitors of the human 12/15 lipoxygenase enzyme, which contributes to brain injury after a stroke by damaging neurons and endothelial cells of the brain. We now want to test our lead compound in a rat model of ischemic stroke, to determine the optimal dosage and time of administration. The effectiveness of the inhibitor will be determined by measuring infarct sizes, as well as the enzyme products formed by 12/15 lipoxygenase in the presence or absence of its inhibitor. These results will then be correlated to the brain exposure achieved by the inhibitor at different dosages. Successful completion of these studies will ready our lead compound for subsequent IND- enabling studies, to advance our lead molecule toward clinical utility as novel stroke therapy.