Therapeutics for age-related macular degeneration

Abstract

The invention provides compositions and methods of predicting a subject's risk of developing age-related macular degeneration (AMD) and methods of treating, delaying, or preventing the development and progression of AMD.

1 . A method of identifying a subject at risk of developing age-related macular degeneration (AMD) comprising:
 providing a test sample from a subject;   measuring in said test sample the levels of interferon-gamma-induced protein-10 (IP-10); and   comparing the levels of IP-10 in said test sample to a reference level of IP-10, wherein a higher level of IP-10 in said test sample compared to the reference level of IP-10 is indicative of AMD.   
     
     
         2 . The method of  claim 1 , wherein said reference level of IP-10 is obtained from one or more individuals that are within two years of age of said subject. 
     
     
         3 . The method of  claim 1 , wherein said identification is prior to the development of clinical signs or phenotype associated with AMD. 
     
     
         4 . The method of  claim 1 , wherein said IP-10 level is measured with an enzyme-linked immunosorbent assay (ELISA). 
     
     
         5 . The method of  claim 1 , wherein said test sample is serum or urine. 
     
     
         6 . The method of  claim 1 , wherein said method further comprises
 measuring in said test sample the levels of eotaxin; and   comparing the levels of eotaxin in said test sample to a reference level of eotaxin, wherein a higher level of eotaxin in said test sample compared to the reference level of eotaxin is indicative of AMD.   
     
     
         7 . A method of identifying a subject at risk of developing AMD comprising:
 providing a test sample from a subject;   measuring in said test sample the levels of eotaxin; and   comparing the levels of eotaxin in said test sample to a reference level of eotaxin, wherein a higher level of eotaxin in said test sample compared to the reference level of eotaxin is indicative of AMD.   
     
     
         8 . The method of  claim 7 , wherein said reference level of eotaxin is obtained from one or more individuals that are within two years of age of said subject. 
     
     
         9 . The method of  claim 7 , wherein said identification is prior to the development of clinical signs or phenotype associated with AMD. 
     
     
         10 . The method of  claim 7 , wherein said eotaxin level is measured with an ELISA. 
     
     
         11 . The method of  claim 7 , wherein said test sample is serum or urine. 
     
     
         12 . A method of treating AMD in a subject comprising administering to said subject a composition that inhibits the activity of IP-10. 
     
     
         13 . The method of  claim 12 , wherein said AMD is dry AMD. 
     
     
         14 . The method of  claim 12 , wherein said AMD is wet AMD. 
     
     
         15 . The method of  claim 12 , wherein said composition that inhibits the activity of IP-10 is a neutralizing antibody or a solubilized receptor that binds circulating IP-10, or a CXCR3 receptor antagonist. 
     
     
         16 . The method of  claim 12 , wherein said composition is administered intravenously, subcutaneously, or orally. 
     
     
         17 . The method of  claim 12 , wherein said composition is administered locally, topically, intraocularly, periburlbarly, or intravitreally. 
     
     
         18 . The method of  claim 12 , wherein said composition comprises a non-selective cytokine inhibitor that has cross-over inhibitory activity against IP-10 or eotaxin receptors. 
     
     
         19 . The method of  claim 15 , wherein said CXCR3 receptor antagonist is selected from the group consisting of NBI-74330, NSC651016, LMP420, AZD3778, T0906487, AMG487, TAK779, and NBI-74330. 
     
     
         20 . The method of  claim 12 , wherein said method further comprises administering to said subject a composition that inhibits the activity of eotaxin. 
     
     
         21 . A method of treating AMD in a subject comprising administering to said subject a composition that inhibits the activity of eotaxin. 
     
     
         22 . The method of  claim 21 , wherein said AMD is dry AMD. 
     
     
         23 . The method of  claim 21 , wherein said AMD is wet AMD. 
     
     
         24 . The method of  claim 21 , wherein said composition that inhibits the activity of eotaxin is a neutralizing antibody or a solubilized receptor that binds circulating eotaxin, or a CC receptor antagonist. 
     
     
         25 . The method of  claim 21 , wherein said composition is administered orally, intravenously or subcutaneously. 
     
     
         26 . The method of  claim 21 , wherein said composition is administered locally, topically, intraocularly, periburlbarly, intravitreally. 
     
     
         27 . The method of  claim 21 , wherein the composition comprises a non-selective cytokine inhibitor that has cross-over inhibitory activity against IP-10 or eotaxin receptors. 
     
     
         28 . The method of  claim 21 , wherein the composition that inhibits the activity of eotaxin is a CCR3 receptor antagonist selected from the group consisting of DPC168, BMS570520, Ki19003, SB328437, GW701897, YM-344031 and GW766994. 
     
     
         29 . The method of  claim 21 , wherein the composition inhibits TNF-α and IP-10. 
     
     
         30 . The method of  claim 21 , wherein the composition that inhibits the activity of eotaxin is LMP-420. 
     
     
         31 . A method of preventing AMD in a subject at risk thereof comprising administering to said subject a composition that inhibits the activity of IP-10. 
     
     
         32 . A method of preventing AMD in a subject at risk thereof comprising administering to said subject a composition that inhibits the activity of eotaxin. 
     
     
         33 . A method of monitoring treatment of AMD comprising:
 (a) providing a test sample from a subject;   (b) measuring in said test sample the levels of IP-10;   (c) administering to said subject a composition that inhibits the activity of IP-10;   (d) providing a second test sample from a subject;   (e) measuring in said second test sample the levels of IP-10;   (f) comparing the levels of IP-10 in said second test sample to the levels of IP-10 in said first test sample, wherein a higher level of IP-10 in said first test sample compared to said second sample indicates said treatment is effective.   
     
     
         34 . A kit for identifying a subject at risk of developing AMD comprising:
 a first reagent that detects IP-10;   a second reagent that detects eotaxin; and   directions for using said kit.   
     
     
         35 . A nomogram comprising a plurality of numerical relations correlating the levels of IP-10 and eotaxin in a bodily fluid to the risk of developing AMD.