Diagnostics and Therapeutics for Macular Degeneration-Related Disorders

Abstract

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

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 age-related macular disorder (AMD), North Carolina macular dystrophy, Sorsby's fundus dystrophy, Stargardt's disease, pattern dystrophy, Best disease, dominant drusen, malattia leventinese, retinal detachment, chorioretinal degenerations, retinal degenerations, photoreceptor degenerations, RPE degenerations, mucopolysaccharidoses, rod-cone dystrophies, cone-rod dystrophies, and cone degenerations. 
     
     
         7 - 8 . (canceled) 
     
     
         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 . (canceled) 
     
     
         13 . The method of  claim 11 , wherein said complement pathway associated molecule is haptoglobin, Ig kappa chain, Ig lambda chain, Ig gamma chain, clusterin, C6 or C5b-C9 complex. 
     
     
         14 . (canceled) 
     
     
         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 - 17 . (canceled) 
     
     
         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 using an assay such as a hemolysis assay, T cell proliferative assay, DTH assay, or an immunological assay. 
     
     
         19 . (canceled) 
     
     
         20 . A method for treating or preventing the development of a macular degeneration in a subject, comprising administering 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 complement 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 or is known to be at risk for developing a macular degeneration-related disorder. 
     
     
         22 . (canceled) 
     
     
         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 age-related macular disorder, North Carolina macular dystrophy, Sorsby's fundus dystrophy, Stargardt's disease, pattern dystrophy, Best disease, dominant drusen, malattia leventinese, retinal detachment, chorioretinal degenerations, retinal degenerations, photoreceptor degenerations, RPE degenerations, mucopolysaccharidoses, rod-cone dystrophies, cone-rod dystrophies, and cone degenerations. 
     
     
         25 - 26 . (canceled) 
     
     
         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 of said complement pathway associated molecule. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 20 , wherein said agent modulates an enzymatic activity of a complement protein or a complement pathway associated molecule, such as 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. 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 30 , wherein said agent modulates a cellular activity responsive to or mediated by activation of complement system, such as cell lysis. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled)