Preclinical Validation of Human Apyrase in Stroke Models

DESCRIPTION (provided by applicant): Human apyrase represents a highly promising therapy for acute ischemic stroke which is a leading cause of death and disability with almost no effective therapy for most patients. This enzyme strongly inhibits platelet activation and aggregation with modest bleeding risk. Using a protein informatics approach, we have successfully engineered a human apyrase, APT102, which exhibits significantly higher enzymatic activity and platelet inhibition than the wild-type apyrases. Importantly, APT102 conferred cerebroprotection against experimental stroke without inducing intracerebral hemorrhage. With the Phase I grant support, we will develop a process for high-yield purification of APT102. We will then utilize clinically relevant embolic model to validate whether APT102 provides significant neuroprotective effect without increased bleeding risk. Human apyrase represents a highly promising therapy for acute ischemic stroke. We will utilize a clinically relevant embolic model to validate whether the protein provides significant neuroprotective effect without increased bleeding risk.