Abstract: This invention provides for a method for inhibiting new tissue growth in blood vessels in a subject, wherein the subject experienced blood vessel injury, which comprises administering to the subject a pharmaceutically effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE) so as to inhibit new tissue growth in the subject's blood vessels. The invention also provides for method for inhibiting neointimal formation in blood vessels in a subject, wherein the subject experienced blood vessel injury, which comprises administering to the subject a pharmaceutically effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE) so as to inhibit neointimal formation in the subject's blood vessels.

Abstract: The present invention provides a method for treating symptoms of diabetes in a diabetic subject which comprises administering to the subject a therapeutically effective amount of an agent which inhibits binding of advanced glycation endproducts to any receptor for advanced glycation endproducts so as to treat chronic symptoms of diabetes in the subject.

Abstract: The present invention provides for an isolated human EN-RAGE peptide. The present invention also provides for a method for determining whether a compound is capable of inhibiting the interaction of an EN-RAGE peptide with a RAGE peptide, which comprises: (a) admixing: (i) a RAGE peptide or an sRAGE peptide or a fragment of either thereof, (ii) an EN-RAGE peptide or a fragment thereof, and (iii) the compound; (b) measuring the level of interaction between the peptide of step (a) (i) and the peptide of step (a) (ii), and (c) comparing the amount of interaction measured in step (b) with the amount measured between the petpide of step (a)(i) and the peptide of step (a) (ii) in the absence of the compound, thereby determining whether the compound is capable of inhibiting the interaction of the EN-RAGE peptide with the RAGE peptide, wherein a reduction in the amount of interaction in the presence of the compound indicates that the compound is capable of inhibiting the interaction.

Abstract: This invention provides a polypeptide consisting essentially of all or a portion of the cytoplasmic domain of RAGE. This invention further provides a polypeptide consisting essentially of a portion of Diaphanous that binds to the cytoplasmic domain of RAGE. Additionally, this invention provides related nucleic acids, vectors, cells and methods.

Abstract: Disclosed are RAGE fusion proteins comprising RAGE polypeptide sequences linked to a second, non-RAGE polypeptide. The RAGE fusion protein may utilize a RAGE polypeptide domain comprising a RAGE ligand binding site and an interdomain linker directly linked to an immunoglobulin CH2 domain. Such fusion proteins may provide specific, high affinity binding to RAGE ligands. Also disclosed is the use of the RAGE fusion proteins as therapeutics for RAGE-mediated pathologies.

Abstract: The present invention provides for a method to prevent accelerated atherosclerosis in a subject predisposed thereto which comprises administering to the subject a polypeptide derived from soluble receptor for advanced glycation endproduct in an amount effective to prevent accelerated atherosclerosis in the subject. The present invention also provides for a method to prevent a macrovessel disease in a subject predisposed thereto which comprises administering to the subject a polypeptide derived from soluble receptor for advanced glycation endproduct in an amount effective to prevent macrovessel disease in the subject.

Abstract: This invention provides a method of inhibiting the binding of beta-sheet fibril to RAGE on the surface of a cell which comprises contacting the cell with a binding-inhibiting amount of a compound capable of inhibiting binding of beta-sheet fibril to RAGE so as to thereby inhibit binding of beta-sheet fibril to RAGE. In one embodiment, the beta-sheet fibril is amyloid fibril. In one embodiment, the compound is sRAGE or a fragment thereof. In another embodiment, the compound is an anti-RAGE antibody or portion thereof. This invention provides the above method wherein the inhibition of binding of the beta-sheet fibril to RAGE has the consequences of decreasing the load of beta-sheet fibril in the tissue, inhibiting fibril-induced programmed cell death, and inhibiting fibril-induced cell stress. This invention also provides methods of determining whether a compound inhibits binding of a beta-sheet fibril to RAGE on the surface of a cell.

Abstract: The present invention provides a method for treating inflammation in a subject which comprises administering to the subject soluble receptor for advanced glycation endproduct (sRAGE) in an amount effective to inhibit binding of advanced glycation endproducts (AGEs) to RAGE thereby treating inflammation in the subject. The present invention also provides for a method for treating inflammation in a subject which comprises administering to the subject an agent in an amount effective to inhibit the interaction between receptor for advanced glycation endproduct (RAGE) and its ligand thereby treating inflammation in the subject.

Abstract: This invention provides a method for treating diabetic retinopathy in a subject afflicted therewith, comprising administering to the subject's eyes a therapeutically effective amount of soluble RAGE or a derivative thereof, thereby treating diabetic retinopathy in the subject. This invention further provides a method for inhibiting the onset of diabetic retinopathy in a subject afflicted therewith, comprising administering a prophylactically effective amount of soluble RAGE or a derivative thereof to the subject's eyes, thereby inhibiting the onset of diabetic retinopathy in the subject.

Abstract: This invention provides for a method for inhibiting new tissue growth in blood vessels in a subject, wherein the subject experienced blood vessel injury, which comprises administering to the subject a pharmaceutically effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE) so as to inhibit new tissue growth in the subject's blood vessels. The invention also provides for method for inhibiting neointimal formation in blood vessels in a subject, wherein the subject experienced blood vessel injury, which comprises administering to the subject a pharmaceutically effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE) so as to inhibit neointimal formation in the subject's blood vessels.

Abstract: The present invention provides a method for treating inflammation in a subject which comprises administering to the subject soluble receptor for advanced glycation endproduct (sRAGE) in an amount effective to inhibit binding of advanced glycation endproducts (AGEs) to RAGE thereby treating inflammation in the subject. The present invention also provides for a method for treating inflammation in a subject which comprises administering to the subject an agent in an amount effective to inhibit the interaction between receptor for advanced glycation endproduct (RAGE) and its ligand thereby treating inflammation in the subject.

Abstract: The present invention provides for a method for inhibiting tumor invasion or metastasis in a subject which comprises administering to the subject a therapeutically effective amount of a form of soluble Receptor for Advanced Glycation Endproducts (RAGE). The present invention also provides a method for evaluating the ability of an agent to inhibit tumor invasion in a local cellular environment which comprises: (a) admixing with cell culture media an effective amount of the agent; (b) contacting a tumor cell in cell culture with the media from step (a); (c) determining the amount of spreading of the tumor cell culture, and (d) comparing the amount of spreading of the tumor cell culture determined in step (c) with the amount determined in the absence of the agent, thus evaluating the ability of the agent to inhibit tumor invasion in the local cellular environment.

Abstract: The present invention provides for a method to prevent accelerated atherosclerosis in a subject predisposed thereto which comprises administering to the subject a polypeptide derived from soluble receptor for advanced glycation endproduct in an amount effective to prevent accelerated atherosclerosis in the subject. The present invention also provides for a method to prevent a macrovessel disease in a subject predisposed thereto which comprises administering to the subject a polypeptide derived from soluble receptor for advanced glycation endproduct in an amount effective to prevent macrovessel disease in the subject.

Abstract: The present invention provides for an isolated human EN-RAGE peptide. The present invention also provides for a method for determining whether a compound is capable of inhibiting the interaction of an EN-RAGE peptide with a RAGE peptide, which comprises: (a) admixing: (i) a RAGE peptide or an sRAGE peptide or a fragment of either thereof, (ii) an EN-RAGE peptide or a fragment thereof, and (iii) the compound; (b) measuring the level of interaction between the peptide of step (a)(i) and the peptide of step (a)(ii), and (c) comparing the amount of interaction meausred in step (b) with the amount measured between the peptide of step (a) (i) and the peptide of step (a) (ii) in the absence of the compound, thereby determining whether the compound is capable of inhibiting the interaction of the EN-RAGE peptide with the RAGE peptide, wherein a reduction in the amount of interaction in the presence of the compound indicates that the compound is capable of inhibiting the interaction.

Abstract: The present invention provides for an isolated human EN-RAGE peptide. The present invention also provides for a method for determining whether a compound is capable of inhibiting the interaction of an EN-RAGE peptide with a RAGE peptide, which comprises: (a) admixing: (i) a RAGE peptide or an sRAGE peptide or a fragment of either thereof, (ii) an EN-RAGE peptide or a fragment thereof, and (iii) the compound; (b) measuring the level of interaction between the peptide of step (a) (i) and the peptide of step (a) (ii), and (c) comparing the amount of interaction meausred in step (b) with the amount measured between the petpide of step (a) (i) and the peptide of step (a) (ii) in the absence of the compound, thereby determining whether the compound is capable of inhibiting the interaction of the EN-RAGE peptide with the RAGE peptide, wherein a reduction in the amount of interaction in the presence of the compound indicates that the compound is capable of inhibiting the interaction.

Abstract: The present invention provides a method for decreasing cerebral vasoconstriction in a subject suffering from chronic or acute cerebral amyloid angiopathy which comprises administering to the subject an inhibitor of receptor for advanced glycation endproduct (RAGE) in an effective amount to inhibit transcytosis of amyloid &bgr; peptides across the blood-brain barrier in the subject, thereby decreasing cerebral vasoconstriction in the subject. The invention further provides for a method for ameliorating neurovascular stress in a subject which comprises administering to the subject an effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE), so as to increase cerebral blood flow in the subject, thereby ameliorating neurovascular stress in the subject.

Abstract: The present invention provides a method for treating symptoms of diabetes in a diabetic subject which comprises administering to the subject a therapeutically effective amount of an agent which inhibits binding of advanced glycation endproducts to any receptor for advanced glycation endproducts so as to treat chronic symptoms of diabetes in the subject.

Abstract: The present invention provides a method for treating symptoms of diabetes in a diabetic subject which comprises administering to the subject a therapeutically effective amount of an agent which inhibits binding of advanced glycation endproducts to any receptor for advanced glycation endproducts so as to treat chronic symptoms of diabetes in the subject.

Abstract: The present invention provides a method for determining whether a compound is capable of inhibiting the interaction of a peptide with receptor for advanced glycation end product (RAGE), which comprises: (a) admixing: (i) the peptide, wherein amino groups of the peptide are inactivated by derivitization, (ii) RAGE or a fragment thereof, and (iii) the compound; (b) determining the amount of the peptide bound to RAGE or the fragment thereof, and (c) comparing the amount of bound peptide determined in step (b) with the amount determined when the peptide is admixed with RAGE or a fragment thereof in the absence of the compound, thereby determining whether the compound is capable of inhibiting the interaction of the peptide with RAGE or a fragment thereof, wherein a reduction in the amount of binding in the presence of the compound indicates that the compound is capable of inhibiting the interaction.

Abstract: The present invention provides for an isolated human EN-RAGE peptide. The present invention also provides for a method for determining whether a compound is capable of inhibiting the interaction of an EN-RAGE peptide with a RAGE peptide, which comprises: (a) admixing: (i) a RAGE peptide or an sRAGE peptide or a fragment of either thereof, (ii) an EN-RAGE peptide or a fragment thereof, and (iii) the compound; (b) measuring the level of interaction between the peptide of step (a) (i) and the peptide of step (a) (ii), and (c) comparing the amount of interaction meausred in step (b) with the amount measured between the petpide of step (a)(i) and the peptide of step (a) (ii) in the absence of the compound, thereby determining whether the compound is capable of inhibiting the interaction of the EN-RAGE peptide with the RAGE peptide,, wherein a reduction in the amount of interaction in the presence of the compound indicates that the compound is capable of inhibiting the interaction.