Diagnostics and therapeutics for macular degeneration-related disorders

Abstract

The invention relates to methods for treating, preventing and diagnosing macular degeneration-related disorders.

What is claimed is:  
     
         1 . A method for diagnosing, or identifying a predisposition to the development of, a macular degeneration-related disorder in a subject, comprising detecting in a biological sample from the subject an abnormal activity or an abnormal level of at least one complement pathway associated molecule, or an abnormal cellular activity mediated by the complement pathway.  
     
     
         2 . The method of  claim 1 , wherein said subject is free of complement related diseases other than the macular degeneration-related disorders.  
     
     
         3 . The method of  claim 1 , wherein the detecting further comprises detecting at least one macular degeneration-associated genetic marker, drusen-associated phenotypic marker, or drusen-associated genotypic marker in the subject.  
     
     
         4 . The method of  claim 1 , further comprising examining of the subject with an ophthalmologic procedure.  
     
     
         5 . The method of  claim 4 , wherein said further examining detects damages to the choriocapillaris or RPE of said subject.  
     
     
         6 . The method of  claim 1 , wherein said macular degeneration-related disorder is selected from the group consisting of age-related macular disorder (AMD), North Carolina macular dystrophy, Sorsby's fundus dystrophy, Stargardt's disease, pattern dystrophy, Best disease, dominant drusen, and malattia leventinese.  
     
     
         7 . The method of  claim 1 , wherein said macular degeneration-related disorder is selected from the group consisting of retinal detachment, chorioretinal degenerations, retinal degenerations, photoreceptor degenerations, RPE degenerations, mucopolysaccharidoses, rod-cone dystrophies, cone-rod dystrophies, and cone degenerations.  
     
     
         8 . The method of  claim 1 , wherein said biological sample is eye fluid, urine, blood plasma, serum, or whole blood.  
     
     
         9 . The method of  claim 1 , wherein said abnormal activity is the presence of an autoantibody.  
     
     
         10 . The method of  claim 9 , wherein the autoantibody is directed against a complement pathway associated molecule, a RPE protein, a choroid protein, a retina protein, or a neoantigen.  
     
     
         11 . The method of  claim 1 , wherein the detecting step detects an abnormal level of a complement pathway molecule.  
     
     
         12 . The method of  claim 11 , wherein said abnormal level is detected in urine, blood plasma, serum, whole blood sample, or eye fluid from the subject.  
     
     
         13 . The method of  claim 11 , wherein said complement pathway associated molecule is haptoglobin, Ig kappa chain, Ig lambda chain, or Ig gamma chain.  
     
     
         14 . The method of  claim 11 , wherein said complement pathway molecule is clusterin, C6 or C5b-9 complex.  
     
     
         15 . The method of  claim 1 , wherein the detecting step detects a variant form of a nucleic acid encoding a complement pathway associated protein or an autoantigen.  
     
     
         16 . The method of  claim 15 , wherein said nucleic acid is a mRNA, cDNA, or genomic DNA.  
     
     
         17 . The method of  claim 15 , wherein said variant nucleic acid has a point mutation, a frameshift mutation, or a deletion relative to wild type nucleic acid.  
     
     
         18 . The method of  claim 1 , wherein said abnormal activity is detected by measuring a complement activity in urine, blood plasma, a serum, whole blood sample, or eye fluid from the subject.  
     
     
         19 . The method of  claim 18 , wherein said complement activity is detected by a hemolysis assay, T cell proliferative assay, DTH assay, or an immunological assay.  
     
     
         20 . A method for treating or preventing the development of a macular degeneration in a subject, comprising providing to the subject an effective amount of a therapeutic agent which modulates an activity or expression level of at least one complement pathway associated molecule, or a cellular activity mediated by the compelement pathway, wherein the subject is suffering from or at risk of developing a macular degeneration-related disorder.  
     
     
         21 . The method of  claim 20 , wherein the subject has a macular degeneration-related disorder.  
     
     
         22 . The method of  claim 20 , wherein the subject is at risk of developing a macular degeneration-related disorder.  
     
     
         23 . The method of  claim 20 , wherein said subject is free of other complement related diseases.  
     
     
         24 . The method of  claim 20 , wherein said macular degeneration-related disorder is selected from the group consisting of age-related macular disorder, North Carolina macular dystrophy, Sorsby's fundus dystrophy, Stargardt's disease, pattern dystrophy, Best disease, dominant drusen, and malattia leventinese.  
     
     
         25 . The method of  claim 20 , wherein said macular degeneration-related disorder is selected from the group consisting of retinal detachment, chorioretinal degenerations, retinal degenerations, photoreceptor degenerations, RPE degenerations, mucopolysaccharidoses, rod-cone dystrophies, cone-rod dystrophies, and cone degenerations.  
     
     
         26 . The method of  claim 20 , wherein said agent modulates expression level of a complement pathway associated molecule or a molecule initiating or triggered by the compelement pathway.  
     
     
         27 . The method of  claim 20 , wherein said complement pathway associated molecule is anaphylatoxin C3a, anaphylatoxin C5a, C6, clusterin, haptoglobin, Ig kappa chain, Ig lambda chain, or Ig gamma chain.  
     
     
         28 . The method of  claim 20 , wherein said agent modulates protein expression level of said complement pathway associated molecule.  
     
     
         29 . The method of  claim 28 , furthering comprising detecting said expression level with urine, blood plasma, serum, whole blood, or eye fluid from the subject.  
     
     
         30 . The method of  claim 20 , wherein said agent modulates an enzymatic activity of a complement protein or a complement pathway associated molecule.  
     
     
         31 . The method of  claim 30 , wherein said enzymatic activity is catalysis of conversion of C3 into C3a and C3b, conversion of C5 into C5a and C5b, or cleavage of Factor B into Ba and Bb.  
     
     
         32 . The method of  claim 30 , furthering comprising detecting said activity by a hemolytic assay, T cell proliferative assay, DTH assay, or an immunological assay.  
     
     
         33 . The method of  claim 30  wherein said activity is detected with urine, blood plasma, serum, whole blood, or eye fluid from the subject.  
     
     
         34 . The method of  claim 30 , wherein said agent modulates a cellular activity responsive to or mediated by activation of complement system.  
     
     
         35 . The method of  claim 34 , wherein said cellular activity is cell lysis.  
     
     
         36 . The method of  claim 34 , furthering comprising detecting said cellular activity by a hemolysis assay.  
     
     
         37 . The method of  claim 34 , wherein said cellular activity is detected with urine, blood plasma, serum, whole blood, or eye fluid from the subject.