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

a technology of ischemic and reperfusion brain and glp-1, which is applied in the direction of peptide/protein ingredients, metabolic disorders, extracellular fluid disorders, etc., can solve the problems of increasing mortality and morbidity after stroke, causing ischemia, and a two-to-three-fold increase in risk, so as to improve brain anabolism, improve insulin effectiveness, and optimize insulin secretion

Inactive Publication Date: 2010-04-27
ASTRAZENECA PHARMA LP
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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 ...

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...

Method used

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[0047]In accordance with this invention the use of GLP-1 (glucagon-like peptide-1 [7-36] amide) is an ideal alternative to insulin for the treatment of acute stroke. This is because of the glucose-dependent insulinotropic action of GLP-1. Endogenous insulin secretion is stimulated by GLP-1 in the presence of normo- to hyperglycemia, but not during hypoglycemia, thus protecting against the development of severe hypoglycemia. This means that in a type II diabetic, GLP-1 will stimulate a sustained secretion of insulin and will tend to normalize blood glucose levels. Both of these actions can be of enormous benefit in the acute stroke situation. Similar results can be achieved in non-diabetic stroke patients with reactive hyperglycemia. In stroke victims with euglycemia, GLP-1 will result in a modest insulin secretion, which may return to baseline in the absence of supplemental glucose. In such cases, it may be desirable to coadminister intravenous glucose (low-dose, e.g. 5%) in order t...

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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...

Claims

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Application Information

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IPC IPC(8): A61K38/26A61K38/00A61K38/16A61K38/28C07K5/00A61K45/00A61K31/7004A61P9/10
CPCA61K38/26A61P25/00A61P7/00A61P9/10A61K2300/00
Inventor COOLIDGE, THOMAS R.EHLERS, MARIO R. W.
Owner ASTRAZENECA PHARMA LP
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