公开(公告)号：EP1718324A2

公开(公告)日：2006-11-08

申请号：EP04776585.4

申请日：2004-06-14

申请人： Socratech L.L.C. ,  THE UNIVERSITY OF ROCHESTER

发明人： BERISLAV, Zlokovic, V. ,  DEANE, Rashid

IPC分类号： A61K38/02

CPC分类号： G01N33/6896 ,  A61K38/00 ,  C07K14/4711 ,  C07K14/705 ,  G01N33/92 ,  G01N2800/2821

摘要： A soluble derivative of low-density lipoprotein receptor related protein-1 (sLRP-1) binds directly to Alzheimer's amyloid-β peptide (Aβ). This binding may be used to detect Aβ or to separate Aβ from the rest of a subject's body. In Alzheimer's disease, it may be used to provide diagnostic results by detecting Aβ, treatment by removing Aβ, or both.

公开(公告)号：EP1993527A2

公开(公告)日：2008-11-26

申请号：EP07762687.7

申请日：2007-01-26

申请人： THE UNIVERSITY OF ROCHESTER

发明人： ZLOKOVIC, Berislav, V. ,  DEANE, Rashid ,  MILLER, Benjamin, L.

IPC分类号： A61K31/16

CPC分类号： A61K31/166 ,  A61K31/167

摘要： Small molecules are used to inhibit specific receptor-ligand interaction between Alzheimer's amyloid-β peptide (Aβ) and Receptor for Advanced GIy- cation Endproducts (RAGE). Objectives include treating Alzheimer's disease and other pathologies involving cerebral amyloid angiopathy; improving blood flow to or within the brain; decreasing the level of Aβ in the brain; reducing neuropathology associated with Alzheimer's disease; reducing inflammation and/or oxidant stress in the brain; improving memory and/or learning; treating other conditions involving Aβ/RAGE interaction at the blood-brain barrier, RAGE-mediated transport of Aβ into the brain, or RAGE activation in brain vasculature and/or brain parenchyma (e.g., diabetic complications); or any combination thereof.

公开(公告)号：EP1909574A2

公开(公告)日：2008-04-16

申请号：EP06800671.7

申请日：2006-08-03

申请人： Socratech L.L.C. ,  THE UNIVERSITY OF ROCHESTER

发明人： ZLOKOVIC, Berislav, V. ,  WU, Zhenhua ,  DEANE, Rashid

IPC分类号： A01N43/04 ,  C12N15/00 ,  C12N15/63 ,  C07H21/02 ,  C07H21/04

CPC分类号： A61K48/005 ,  A61K48/0075

摘要： Neurovascular disorder critically contributes to the development and pathogenesis of Alzheimer's disease (AD). Transcriptional profiling of human brain endothelial cells (BEC) defines a subset of age-independent genes significantly altered in AD including the homebox gene GAX whose expression controls vascular phenotype and is low in AD. By using viral-mediated GAX gene silencing and transfer, restoring GAX expression in AD BEC is angiogenic, transcriptionally suppresses the AFX1 forkhead transcription factor- mediated apoptosis, and increases the levels of a major amyloid β-peptide (Aβ) clearance receptor, the low density lipoprotein receptor-related protein 1 (LRP- 1) at the blood-brain barrier. In a mouse model of Alzheimer's disease, deletion of the Gax gene results in reductions in brain capillary density and the resting cerebral blood flow, loss of angiogenic brain response to hypoxia, and an impaired Aβ brain efflux caused by reduced LRP-1 levels. The link of GAX gene to AD neurovascular dysfunction provides new mechanistic and therapeutic insights into AD.