Metabolic intervention with GLP-1 or its biologically active analogues to improve the function of the ischemic and reperfused brain

Abstract

It has now been discovered that GLP-1 treatment after acute stroke or hemorrhage, preferably intravenous administration, can be an ideal treatment because it provides a means for optimizing insulin secretion, increasing brain anabolism, enhancing insulin effectiveness by suppressing glucagon, and maintaining euglycemia or mild hypoglycemia with no risk of severe hypoglycemia.

Description

CROSS REFERENCE TO A RELATED APPLICATION[0001]This application is a continuation-in-part of provisional application No. 60 / 103,498 filed Oct. 8, 1998.FIELD OF THE INVENTION[0002]This invention relates to an / effective treatment to improve the function of the ischemic and reperfused brain.BACKGROUND OF THE INVENTION[0003]Strokes, or cerebrovascular accidents, are the result of an acute obstruction of cerebral blood flow to a region of the brain. There are approximately 500,000 cases each year in the United States, of which 30% are fatal, and hence stroke is the third leading cause of death in the United States. Approximately 80% of strokes are “ischemic” and result from an acute occlusion of a cerebral artery (usually a clot or thrombus), with resultant reduction in blood flow. The remainder are “hemorrhagic”, which are due to rupture of a cerebral artery with hemorrhage into brain tissue and consequent obstruction of blood flow due to local tissue compression, creating ischemia.[0004...

AI Technical Summary

Benefits of technology

[0014]It has now been discovered that GLP-1 treatment after acute stroke or hemorrhage, preferably intravenous administration, dan be an ideal treatment because it provides a means for optimizing insulin secretion, increasing brain anabolism, enhancing insulin effectiveness by suppressing glucagon, and maintaining euglycemia or mild hypoglycemia with no risk of severe hypoglycemia or other adverse side effects.

Problems solved by technology

The remainder are “hemorrhagic”, which are due to rupture of a cerebral artery with hemorrhage into brain tissue and consequent obstruction of blood flow due to local tissue compression, creating ischemia.

However, there are additional strong risk factors, of which the most important is diabetes mellitus, which confers a two to three-fold increased risk and is associated with increased mortality and morbidity after stroke.

Moreover, there is strong evidence that hyperglycemia per se, whether associated with diabetes or not, correlates with increased stroke-related mortality and morbidity, although the causal relationship and underlying mechanisms remain controversial.

Because of concerns about safety and variable efficacy, thrombolytic therapy with tPA has not been universally adopted by clinicians treating acute ischemic stroke.

At present, thrombolytic therapy is effectively restricted to major centers with specialized expertise in the management of acute stroke, and it is limited to patients who on CT scanning do not have evidence of major infarction, are less than 70 years old, and are free of major medical conditions including diabetes.

From these considerations it is evident that there is an enormous unmet need for new, effective therapies for acute stroke.

However, the use of insulin is complicated by the uncertainty surrounding the neurotoxic effects of hyperglycemia, the potential benefits of mild-to-modest hypoglycemia, and the potentially lethal effects of severe hypoglycemia.