Compositions and methods for treating macular degeneration

Abstract

Methods of retarding formation of a lipofuscin pigment in the retina and of treating or ameliorating the effects of a disease characterized by an accumulation of a lipofuscin pigment in a retina are provided. These methods include the step of administering to a patient in need thereof a substituted C 20 -retinoid in an amount sufficient to reduce accumulation of a lipofuscin pigment in the retina. Further provided are methods of retarding formation of A2E and/or ATR-dimer by replacing an all-trans-retinal (ATR) substrate with a C 20 -D 3 -retinal substrate under conditions sufficient to impede the formation of A2E. Compositions for retarding formation of a lipofuscin pigment in the retina containing a substituted C 20 -retinoid and a pharmaceutically acceptable carrier are also provided.

1 - 49 . (canceled) 
     
     
         50 . A method of treating a macular degeneration in a subject in need thereof, comprising replacing vitamin A in the subject with an effective amount of a substituted C 20 -D 1-3 -retinoid. 
     
     
         51 . The method according to  claim 50 , wherein the C 20 -D 1-3 -retinoid is selected from the group consisting of C 20 -D 1-3 -retinol, C 20 -D 1-3  retinol ester, C 20 -D 1-3  retinal and C 20 -D 1-3 -pro-vitamin A carotenoids. 
     
     
         52 . The method according to  claim 51 , wherein the C 20 -D 1-3 -retinoid, corresponding to the aldehyde of the C 20 -D 1-3 -retinol acetate, forms A2E in vitro about 7 times slower than non-deuterium-enriched retinoid. 
     
     
         53 . The method according to  claim 51 , wherein the C 20 -D 1-3 -retinoid is selected from the group consisting of C 20 -D 3 -retinol, C 20 -D 3  retinol ester, C 20 -D 3  retinal and C 20 -D 3 -pro-vitamin A carotenoids. 
     
     
         54 . The method according to  claim 53 , wherein the C 20 -D 1-3 -retinoid is C 20 -D 3  retinol acetate. 
     
     
         55 . The method according to  claim 54 , wherein the aldehyde of the C 20 -D 3 -retinol acetate forms A2E in vitro about 7 times slower than non-deuterium-enriched retinol acetate. 
     
     
         56 . The method according to  claim 50 , wherein the pharmaceutical composition is suitable for use as a nutraceutical composition. 
     
     
         57 . The method according to  claim 50 , wherein the macular degeneration is age-related macular degeneration. 
     
     
         58 . The method according to  claim 57 , wherein the macular degeneration is a dry (non-neovascular) age-related macular degeneration. 
     
     
         59 . The method according to  claim 58 , wherein the dry age-related macular degeneration is geographic atrophy (a late stage dry age-related macular degeneration). 
     
     
         60 . The method according to  claim 50 , wherein the macular degeneration is Stargardt disease. 
     
     
         61 . The method according to  claim 50 , wherein the macular degeneration is selected from the group consisting of Vitelliform or Best disease, Sorsby's fundus dystrophy, retinitis pigmentosa, and Malattia Leventinese. 
     
     
         62 . The method according to  claim 57 , wherein the pharmaceutical composition comprises C 20 -D 3 -retinol acetate. 
     
     
         63 . The method according to  claim 60  wherein the pharmaceutical composition comprises C 20 -D 3 -retinol acetate. 
     
     
         64 . The method according to  claim 61 , wherein the pharmaceutical composition comprises C 20 -D 3 -retinol acetate.