Method of enhancing lysosomal alpha-Galactosidase A

Patent metadata

Field	Value
Publication number	US-2016346262-A1
Application number	US-201615005371-A
Country	US
Kind code	A1
Filing date	Jan 25, 2016
Priority date	Jun 1, 1998
Publication date	Dec 1, 2016
Grant date	—

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.

First claim

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.

Assignees

• Icahn School Med Mount Sinai

Inventors

• Fan Jian-Qiang
• Ishii Satoshi

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P13/12

  of the kidneys · CPC title

• C12N9/2465

  acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22) · CPC title

• A61K31/70

  Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) · CPC title