Methods and Reagents for Treatment and Diagnosis of Vascular Disorders and Age-Related Macular Degeneration

Abstract

Disclosed are screening methods for determining a human subject's propensity to develop a vascular disorder and/or age-related macular degeneration (AMD), therapeutic or prophylactic compounds for treating disease or inhibiting its development, and methods of treating patients to alleviate symptoms of the disease, prevent or delay its onset, or inhibit its progression. The inventions are based on the discovery that persons with a genome having a deletion of the CFHR-1 and/or CFHR-3 gene, which normally lie on human chromosome 1 between DNA encoding CFH and CFHR-4, are at reduced risk of developing AMD, and elevated risk of developing vascular disease such as aneurysm.

1 .- 44 . (canceled) 
     
     
         45 . A method of treating a subject having age-related macular degeneration (AMD) or at risk of developing AMD, the method comprising:
 administering to the subject an antibody that specifically binds a CFHR1 protein of SEQ ID NO:4, wherein the antibody binds an epitope encoded in residues 1 to 143 of SEQ ID NO:4 and does not bind to any of CFH, CFHT, CFHR2, CFHR3, CFHR4 or CFHR5.   
     
     
         46 . The method of  claim 45 , comprising administering the antibody of  claim 45  and that specifically binds a protein encoded by the CFHR3 gene. 
     
     
         47 . The method of  claim 45 , wherein the antibody is monoclonal. 
     
     
         48 . The method of  claim 45 , wherein the antibody is a human or a humanized antibody. 
     
     
         49 . A kit that includes:
 (1) a pharmaceutical product comprising an antibody that specifically binds CFHR1 protein (SEQ. ID NO:4) and does not bind to any of CFH, CFHT, CFHR2, CFHR3, CFHR4 or CFHR5, formulated in a pharmaceutically acceptable excipient in an amount sufficient to achieve a plasma concentration of CFHR1 protein that is between 50 to 600 micrograms/mL in a human subject in need thereof; and   (2) instructions for use of the antibody for treating age-related macular degeneration (AMD).