Methods and Reagents for Treatment of Age-Related Macular Degeneration

Abstract

The invention relates to Factor H gene polymorphisms and haplotypes associated with an elevated or a reduced risk of AMD. The invention provides methods and reagents for diagnosis and treatment of AMD.

1 - 60 . (canceled) 
     
     
         61 . A method of treating a human patient in need of treatment for age-related macular degeneration (AMD) comprising introducing into at least some of the cells of the patient an exogenous polynucleotide selected from the group consisting of
 (a) a polynucleotide encoding for native Complement Factor H (CFH) polypeptide, said polypeptide having at least 90% identity to SEQ. ID No. 2, or an active fragment thereof;   (b) a polynucleotide encoding for CFH polypeptide with the proviso that residue 402, numbered relative to SEQ. ID No. 2, is tyrosine, said polypeptide having at least 90% identity to SEQ. ID No. 2, or an active fragment thereof;   (c) a polynucleotide encoding for CFH polypeptide with the proviso that residue 62, is isoleucine, numbered relative to SEQ. ID No. 2, said polypeptide having at least 90% identity to SEQ. ID No. 2;   (d) purified anti-sense RNA complementary to a RNA encoding for CFH polypeptide with the proviso that at residue 402, numbered relative to SEQ. ID No. 2, said polypeptide having at least 90% identity to SEQ. ID No. 2, or an active fragment thereof;   (e) siRNA that interferes with the expression of a CFH polypeptide which makes one more susceptible to AMD; and   (f) a polynucleotide encoding for native Complement Factor H Related 5 (CFHR5) polypeptide, said polypeptide having at least 90% identity to SEQ. ID No. 8, or an active fragment thereof.   
     
     
         62 . The method of  claim 61  wherein the exogenous polynucleotide is a gene therapy vector comprising (i) a nucleic acid sequence encoding a CFH polypeptide and (ii) a promoter operably linked to said nucleic acid sequence. 
     
     
         63 . The method of  claim 62  wherein the CFH polypeptide is complement factor H or a complement factor H-like 1. 
     
     
         64 . The method of  claim 61 , comprising introducing into cells of the patient an exogenous polynucleotide sequence encoding a Complement Factor H (CFH) polypeptide, wherein the CFH polypeptide (i) has a sequence with at least 90% sequence identity to SEQ ID NO:2, comprises tyrosine at residue 402 numbered relative to SEQ ID NO:2, and binds to complement component 3b (C3b), or (ii) has a sequence with at least 90% sequence identity to SEQ ID NO:4, comprises tyrosine at residue 402 numbered relative to SEQ ID NO:2, and binds to complement component 3b (C3b). 
     
     
         65 . The method of  claim 64  wherein the CFH polypeptide comprises isoleucine at residue 62, numbered relative to SEQ ID NO:2. 
     
     
         66 . The method of  claim 65  wherein the CFH polypeptide comprises residues 19-1231 of SEQ ID NO:5. 
     
     
         67 . The method of  claim 65  wherein the CFH polypeptide comprises residues 19-449 of SEQ ID NO:6. 
     
     
         68 . The method of  claim 64  wherein the cells are in the retina. 
     
     
         69 . The method of  claim 65  wherein both CFH gene alleles in the patient's genome encode histidine at position 402. 
     
     
         70 . The method of  claim 64 , wherein introducing comprises administering to the patient a recombinant vector comprising a polynucleotide sequence encoding the CFH polypeptide and an operably linked promoter. 
     
     
         71 . The method of  claim 70 , wherein the vector is introduced by injection into the eye. 
     
     
         72 . The method of  claim 70  wherein the promoter is a promoter that drives expression in the retinal pigment epithelium (RPE). 
     
     
         73 . The method of  claim 61  wherein the patient has signs or symptoms of AMD. 
     
     
         74 . The method of  claim 73  wherein the patient has been diagnosed with early stage AMD. 
     
     
         75 . The method of  claim 73  wherein the patient shows signs of drusen development. 
     
     
         76 . The method of  claim 61  wherein the patient has been diagnosed as having a propensity to develop AMD.