Preventing Neurovascular Matrix Degradation and Hemorrhage in Acute Ischemic Stroke

Seventeen million people each year suffer from an ischemic stroke and millions are left dead and disabledTreatment with recombinant tissue plasminogen activatorr tPAis only modestly effective at reducing disability and it is associated with brain hemorrhage in up toof patients when serial imaging studies are performedBrain hemorrhage causes death and disability andis the major cause of early mortality in r tPA treated patientsthere is no proven effective therapyStentriever therapy improves reperfusion in ischemic strokebut it is only available for a minority of patients and it carries a comparable risk of intracranial hemorrhageA safe treatment for ischemic strokeused alone or combination with these therapieswhich reduces hemorrhageas well as brain infarction and brain edema could save livesreduce patient disability and lower health care costsTo address this needTranslational SciencesIncseeks to convert a leadhigh affinityultra specific matrix metalloproteinaseinhibitorMMPiinto an optimal therapy for strokeMMPis a protease induced by ischemia or r tPA therapywhich degrades the extracellular and the neurovascular matrixMMPis induced by brain ischemia and by r tPA therapythere is abundant evidence that MMPcontributes to ischemic brain injury including bleeding during ischemic strokePre clinical proof of concept datafrom multiple laboratoriesin a number of species and modelsshows that inhibiting the action of MMPsignificantly reduces ischemic brain infarction and disabilityExperimental evidence shows that when the lead MMPi is added to r tPA therapy it markedly reduces brain hemorrhageinfarctionswellingneurobehavioral disability and death in experimental ischemic strokeDue to its exquisite potency and specificitythis MMPi has extraordinary therapeutic potential for reducing morbidity and mortality without causing the serious adverse events associated with broad spectrum MMP inhibitorsThe goal of this Phase I proposal is to follow FDA guidance to convert this potentspecific lead MMPi into a humanizedfirst in class therapy for ischemic stroke Current therapy for ischemic stroke only benefits a minority of patients because it causes serious complications such as bleedingWe are developing an ultra specifichigh potency therapeutic agent thatin experimental studiessignificantly reduces bleeding and mortality when given with current stroke treatmentThis new agent has the potential to significantly improve outcomes for patients with ischemic stroke