Beta-amyloid binding factors and inhibitors thereof
OwnerChi-Bom Chae, Yong Song Gho +4inventors
InventorsChi-Bom Chae, Yong Song Gho, Seung-Pil Yang, Byung Oh Kwon, Dong-Goo Bac, Sewook Hwang
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Abstract
The present invention relates to a VEGF polypeptide that binds to β-amyloid. The present invention also relates to a compound that sequesters β-amyloid. And conversely, the invention relates to a compound that sequesters VEGF. Thus, the present invention also relates to a method of screening for a compound that inhibits the binding of VEGF to β-amyloid, and thus relates to diagnosis and treatment of Alzheimer's Disease.
Claims37
A β-amyloid binding polypeptide (β-ABP) that specifically binds heparin and β-amyloid, wherein the polypeptide is not SEQ ID NO:5.
A method of preventing binding between β-amyloid and endogenous VEGF, comprising:
- (a) generating a recombinant viral or plasmid vector comprising a DNA sequence encoding VEGF polypeptide operatively linked to a promoter;
- and
- (b) administering the viral or plasmid vector to a patient in need thereof, such that expression of said DNA sequence within a brain results in binding between β-amyloid and VEGF polypeptide.
A method of inactivating endogenous VEGF in a region of excessive angiogenesis, comprising:
- (a) generating a recombinant viral or plasmid vector comprising a DNA sequence encoding B-amyloid polypeptide operatively linked to a promoter;
- and
- (b) administering the viral or plasmid vector to a patient in need thereof, such that expression of said DNA sequence at the site of excessive angiogenesis results in binding between the β-amyloid polypeptide and endogenous VEGF.
A method of determining binding of VEGF polypeptide to β-amyloid comprising:
- (a) providing VEGF to a sample suspected of containing β-amyloid;
- and
- (b) detecting binding of VEGF to the β-amyloid, if β-amyloid is present in the sample.
A method of diagnosing a disease that is indicated by presence of amyloid plaques, comprising:
- (a) providing a sample tissue that is suspected of having amyloid plaques;
- (b) contacting said sample tissue with a VEGF polypeptide, which is capable of specifically binding to β-amyloid;
- and
- (c) detecting the binding of said polypeptide with said amyloid plaques, wherein binding indicates diseased state.
A diagnostic kit comprising:
- (a) a container comprising a VEGF polypeptide that specifically binds β-amyloid;
- (b) a first ligand that specifically binds to said VEGF polypeptide, β-amyloid, or polypeptide/β-amyloid complex;
- (c) a labeled second ligand that specifically binds to said first ligand;
- and instructions for its use.
A method of preventing binding between VEGF and β-amyloid, comprising providing a compound which inhibits the interaction between VEGF and β-amyloid.
A method of screening for a compound which inhibits VEGF/β-amyloid binding, comprising
- (a) contacting a compound with a sample containing VEGF and β-amyloid;
- (b) determining level of VEGF and β-amyloid binding under conditions in which VEGF and β-amyloid normally specifically bind to each other;
- (c) determining level of VEGF and β-amyloid binding, in the presence of said compound;
- and
- (d) comparing the level of VEGF and β-amyloid binding described in parts (a) and (b), wherein if said level is lower in (c) than in (b), then said compound is an inhibitor of VEGF/β-amyloid binding.
A method of treating Alzheimer's Disease comprising administering to a person in need thereof a therapeutically effective amount of a compound which inhibits binding between VEGF and β-amyloid.
An isolated molecule comprising β-amyloid polypeptide, which is capable of binding VEGF to form a nonfunctional complex comprising:
- (a) a first polypeptide component comprising an amino acid sequence comprising the β-amyloid polypeptide which binds to VEGF;
- and
- (b) a multimerizing component.
An isolated molecule comprising VEGF polypeptide, which is capable of binding β-amyloid to form a nonfunctional complex comprising:
- (a) a first polypeptide component comprising an amino acid sequence comprising the VEGF polypeptide, which binds to β-amyloid polypeptide;
- and
- (b) a multimerizing component.
Dependencies are inferred from the claim text.