Method of enhancing lysosomal alpha-Galactosidase A

Abstract

A method of enhancing the activity of lysosomal α-Galactosidase A (α-Gal A) in mammalian cells and for treatment of Fabry disease by administration of 1-deoxy-galactonojirimycin and related compounds.

1 . A method of enhancing the activity of lysosomal α-galactosidase A in mammalian cells comprising administering an effective amount of a compound selected from the group consisting of 2,5-dideoxy-2,5-imino-D-mannitol, 3,4-diepz-α-homonojirimycin, 5-O-α-D-galactopyranosyl-α-homonojirimycin, 1-deoxygalactonojirimycin, 4-epi-fagomine, calystegine A3, calystegine B2, and calystegine B3, and N-alkyl derivatives thereof. 
     
     
         2 . The method of  claim 1  wherein the lysosomal α-galactosidase A is a mutant form which is present in patients with Fabry disease. 
     
     
         3 . The method of  claim 1  wherein said cells are human cells. 
     
     
         4 . The method of  claim 3  wherein said cells are the cells of a patient with Fabry disease. 
     
     
         5 . A method of treating Fabry disease comprising administering an effective amount of a compound selected from the group consisting of 2,5-dideoxy-2,5-imino-D-mannitol, 3,4-diepi-α-homonojirimycin, 5-O-α-D-galactopyranosyl-α-homonojirimycin, 1-deoxygalactonojirimycin, 4-epi-fagomine, calystegine A3, calystegine B2, and calystegine B3, and N-alkyl derivatives thereof. 
     
     
         6 . The method of  claim 5  wherein said compound is 1-deoxygalactonojirimycin or 3,4-diepi-α-homonojirimycin. 
     
     
         7 . The method of  claim 6  wherein said compound is 1-deoxygalactonojirimycin. 
     
     
         8 . (canceled) 
     
     
         9 . A method of treating Fabry disease comprising administering an effective amount of a compound of the formula 
       
         
           
           
               
               
           
         
       
       wherein R 1  represents H, —CH 2 —or CH 2 OH;
 R 2  represents H, OH or —O-galactose; 
 R 3  and R 4  independently represent H, or OH; 
 R 5  represents H, or —CH 2 —; 
 R 6  represents CH 2 OH, or OH; and 
 R 7  represents H or an alkyl group containing 1-3 carbon atoms, provided that when either R 1 , or R 5  is —CH 2 —, they are identical and are linked to form a second ring structure.