Project Summary/Abstract
The aging of the population in industrialized nations is increasing the number of ischemic strokes that present in
the emergency rooms of hospitals. In the ischemic stroke neurons die rapidly (estimated at 1 million neurons per
minute) prompting the need for rapid triage and treatment to open the blocked blood vessel. We have previously
established that the exact rate at which neurons die and size of the infarction grows is highly variable among
patients and depends strongly on the degree of leptomeningeal arterial collateralization. The goal of this proposal
is to test a new biopharmaceutical agent (Sanguinate®) that is designed to boost the collateralization in ischemic
stroke as well as deliver and release oxygen locally in tissue with low oxygen tension. We believe that this
approach will reduce infarct volume in all strokes and reduce reperfusion injury in those successfully recanalized
by during interventional procedures. Sanguinate® is an investigational bio-pharmaceutical blood substitute that
facilitates the transfer of oxygen to oxygen-deprived cells and tissues. Sanguinate’s unique oxygen-delivery
system has the potential to treat hypoxia/ischemia. Sanguinate® is purified bovine hemoglobin that has been
pegylated and combined with carbon monoxide to suppress vasoconstriction and provide anti-inflammatory
effects. The bovine hemoglobin then carries oxygen for targeted release to areas with a low partial pressure of
oxygen (ischemic tissue). It has been shown to successfully address detrimental vasoconstrictive side effects
associated with older generation artificial blood products, but the effect on tissue perfusion, infarct volumes,
infarct growth and tissue hypoxia and have not been directly measured. The rationale for this work is that brain
infarcts grow rapidly if a blood vessel feeding the brain is blocked and even with the most efficient triage and
shortest door-to-needle time, millions of neurons will die. There is an unmet need for an easy, safe i.v. infusion
that can stop to growth of an infract and unlike thrombolytic agents, be safely administered to all patients as soon
as symptoms arise. We will establish the effectiveness of a new pharmaceutical that can be easily deployed in
emergency rooms, ambulances and satellite hospitals prior to transfer to a stroke center comparing doses and
time-to-treatment effect with serial imaging a biomarkers of brain damage and inflammation in a controlled model
of ischemic stroke. Our findings will elucidate the mechanism of action of the agent and inform the design of
future human clinical trials.
