Media.Player

PEG-Albumin: New Therapeutics for Ischemic Stroke

详细技术说明

Project ID: D2014-54 Background: Ischemic stroke is the fourth leading cause of death in the US and a leading cause of significant disability. Large strokes account for the majority of deaths during the first week of ischemic insult. Although common, current management of strokes remains suboptimal in improving patients’ overall outcomes. Apart from neurosurgical interventions which are too invasive, non-surgical approaches such as bed elevation to facilitate venous drainage, hyperventilation to decrease pCO2 to cause vasoconstriction, and osmotic therapy such as 3% NaCl and mannitol to decrease intracranial pressure (ICP) have not shown persistent effects or improved outcomes.  All this has led to a high unmet need for an effective therapeutic agent for treatment of ischemic stroke. Invention Description:Researchers at the University of Toledo have addressed the need of effective ischemic stroke medication by developing the use of polyethylene glycol modified albumin (PEG-Albumin) in ischemic stroke. It is known that ischemic cerebral edema peaks 3-5 days following ischemic insult and this correlates with the peak of Blood Brain Barrier (BBB). Before BBB disruption, the ischemic tissues or the core ischemic zone and the surrounding critically hypo perfused (yet salvageable) area or the penumbra experience different changes in the process of cerebral infract development. The cells in these regions have been shown to undergo apoptosis. Whereas ischemia most often results in necrosis of neurons in core zone, brain cells in penumbra region may remain viable for several hours. This makes penumbra region most effective for pharmacologic interventions. Any attenuation of the penumbra area surrounding the infarct core may help in improving its perfusion and limiting the infract area to the ischemic core, thus rescuing the surrounding tissues.  Our inventors have demonstrated that maintaining enough PEG-Albumin inhibits endothelial cell apoptosis which leads to salvage of the penumbra region. Using a mouse model of permanent middle cerebral artery cauterization to induce ischemic stroke, they studied the effects of PEG-Albumin in 3% hypertonic saline (HS) solution on ischemic damage and neurological deficits reduction and compared the results with two other osmotic therapies, 3% HS solution and human serum albumin (HAS) in 3% HS solution. Via this study, they established that PEG-Albumin reduces the infarct size of mice by 40% as compared to mice treated with HS.  It was also observed that PEG-Albumin was associated with better functional outcomes on neurological deficit scale when compared to HSA. Application:Therapeutic use of PEG-Albumin in treatment of ischemic strokeIP Status: Patent pending

*Abstract

*Principal Investigation

Name: Ragheb Assaly, Assistant Professor

Department: Medicine

Name: J Dignam, Associate Professor

Department: Biochemistry & Molecular Biology

Name: Joseph Shapiro, Dean

Department: Medicine

国家/地区

美国