Compositions and methods for treating galactosemia

Abstract

The disclosure relates to methods for treating galactosemia and manifestations of galactosemia using aldose reductase inhibitors.

1 . A method of treating galactosemia or preventing complications associated with galactosemia, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject in need thereof. 
     
     
         2 . A method of reducing the amount or level of galactitol in a subject with galactosemia, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to the subject. 
     
     
         3 . A method for treating cataracts, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject in need thereof. 
     
     
         4 . The method of  claim 3 , where the subject in need thereof has galactosemia. 
     
     
         5 . A method for treating or preventing cognitive or neurological deficiency associated with galactosemia, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject with galactosemia. 
     
     
         6 . The method of  claim 5 , wherein the cognitive or neurological deficiency associated with galactosemia is speech dysfunction. 
     
     
         7 . The method of  claim 5 , wherein the cognitive or neurological deficiency associated with galactosemia is motor ataxia. 
     
     
         8 . The method of  claim 5 , wherein the cognitive or neurological deficiency associated with galactosemia is cognitive dysfunction. 
     
     
         9 . The method of  claim 5 , wherein the cognitive or neurological deficiency associated with galactosemia is pseudomotor cerebrii. 
     
     
         10 . The method of  claim 5 , wherein the cognitive or neurological deficiency associated with galactosemia is seizure. 
     
     
         11 . The method of  claim 1 , wherein the aldose reductase inhibitor is a compound of any one of Formulas I-III or salt thereof. 
     
     
         12 . The method of  claim 1 , wherein the aldose reductase inhibitor is a zopolrestat or salt thereof, or epalrestat or salt thereof. 
     
     
         13 . The method of  claim 1 , wherein the aldose reductase inhibitor is a compound of Formula (II) or salt thereof. 
     
     
         14 . The method of  claim 13 , wherein the aldose reductase inhibitor is selected from the following or salts thereof 
       
         
           
           
               
               
           
         
       
     
     
         15 . The method of  claim 1 , wherein the aldose reductase inhibitor is a compound of Formula III. 
     
     
         16 . The method of  claim 15 , wherein the aldose reductase inhibitor is selected from the following or salts thereof 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 1 , wherein the subject is a human. 
     
     
         18 . The method of  claim 1 , wherein the galactosemia is manifested in the subject as increased alditol levels in blood, urine or intraocular fluid. 
     
     
         19 . The method of  claim 18 , wherein the alditol is galactitol, myoinositol or sorbitol. 
     
     
         20 . The method of  claim 1 , wherein the galactosemia is manifested in the subject as increased liver cirrhosis, retinal disorder, macular edema, eye cataract, ovarian dysfunction, muscle or nerve dysfunction, retinopathy, neuropathy, impaired neural conduction or mental retardation. 
     
     
         21 . The method of  claim 1 , wherein the galactosemia is Type I Galactosemia (GALT deficiency). 
     
     
         22 . The method of  claim 1 , wherein the galactosemia is Type II Galactosemia (GALK deficiency). 
     
     
         23 . The method of  claim 1 , wherein the galactosemia is Type III Galactosemia (GALE deficiency). 
     
     
         24 . The method of  claim 1 , wherein the aldose reductase inhibitor is Compound A or a salt thereof. 
     
     
         25 . The method of  claim 1 , wherein the aldose reductase inhibitor is Compound B or a salt thereof.