Method of enhancing lysosomal α-galactosidase A
View Patent ↗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 to cells with low endogenous α-galactosidase A activity an effective amount of an N-alkyl derivative of 1-deoxygalactonojirimycin, wherein the endogenous α-galactosidase A expressed by the cells is a mutant α-galactosidase A.
2. The method of claim 1 wherein said cells are human cells.
3. The method of claim 2 wherein said cells are the cells of a patient with Fabry disease.
4. A method of enhancing the activity of lysosomal α-galactosidase A in mammalian cells comprising administering to cells with low endogenous α-galactosidase A activity an effective amount of a compound of formula 1
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, wherein the compound of formula 1 is not 1-deoxygalactonojirimycin, and wherein the endogenous α-galactosidase A expressed by the cells is a mutant α-galactosidase A.
5. The method of claim 1 , wherein the low α-galactosidase A activity expressed by the mammalian cells is less than 30% of α-galactosidase A activity of a cell expressing a non-mutant α-galactosidase A.
6. The method of claim 4 , wherein the low α-galactosidase A activity expressed by the mammalian cells is less than 30% of α-galactosidase A activity of a cell expressing a non-mutant α-galactosidase A.