Compositions and methods for stimulating amyloid removal in amyloidogenic diseases using advanced glycosylation endproducts

摘要

PCT No. PCT/US95/01380 Sec. 371 Date Aug. 10, 1996 Sec. 102(e) Date Aug. 10, 1996 PCT Filed Feb. 2, 1995 PCT Pub. No. WO95/20979 PCT Pub. Date Aug. 10, 1995The present invention relates generally to methods and compositions for treating amyloidogenic diseases such as Alzheimer's disease and the development of type II diabetes, in which deposition of amyloid in organs such as the brain and pancreas interfere with neurological function and insulin release, respectively. The methods and compositions are directed toward increasing the activity of scavenger cells within the body at recognizing and removing amyloid deposits from affected tissues and organs. Scavenger cells may be targeted to amyloid deposits by means of spontaneously-occurring chemical modifications called advanced glycosylation endproducts (AGEs). Compositions are described which increase scavenger cell activity towards AGE-modified amyloid. Amyloid removal may also be enhanced by increasing AGE levels in amyloid deposits within the body by administering AGE-modified amyloid targeting agents, which after becoming situated at sites containing amyloid, subsequently attract scavenger cells to degrade attendant amyloid. These methods and associated compositions result in a decrease in the extent of amyloid deposits in tissues, reducing the attendant pathology.