Method for treating alzheimer's disease using pharmacological chaperones to increase the activity of gangliosidases

• US 9,044,437 B2
• Filed: 10/12/2010
• Issued: 06/02/2015
• Est. Priority Date: 10/19/2009
• Status: Active Grant

• Current Assignee: Amicus Therapeutics, Inc.
• Original Assignee: Amicus Therapeutics, Inc.
• Inventors: Wustman, Brandon, Valenzano, Kenneth, Boyd, Robert
• Primary Examiner(s): CLAYTOR, DEIRDRE RENEE
• Application Number:
  US13/501,586
• Publication Number:
  US 20120309788A1
• Time in Patent Office: 1,694 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/429 condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/7008 Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to a method for treating an individual having Alzheimer'"'"'s Disease by using pharmacological chaperones to increase the activity of gangliosidase and/or sialidase enzymes involved in ganglioside catabolism.

Claims

1. A method for the treatment of Alzheimer'"'"'s Disease in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone that reversibly binds to a gangliosidase selected from the group consisting of:

β

-hexosaminidase A, β

-hexosaminidase B, and β

-hexosaminidase S wherein the pharmacological chaperone is selected from 2-acetamido-1,2-dideoxynojirimycin and N-acetyl-glucosamine-thiazoline.

2. The method of claim 1, wherein the gangliosidase is β

-hexosaminidase B.

3. The method of claim 1, wherein the pharmacological chaperone increases trafficking of gangliosidase from the endoplasmic reticulum into the lysosome, from the endoplasmic reticulum to the cytosol or from the endoplasmic reticulum to the endosomes and the plasma membrane.

4. The method of claim 1, wherein the pharmacological chaperone increases mutant and/or wild-type activity of a gangliosidase.

5. The method of claim 1, wherein the gangliosidase catabolizes gangliosides.

6. The method of claim 5, wherein the gangliosidase is β

-hexosaminidase B and gangliosides are GA2 and GM2.

7. The method of claim 1, wherein the pharmacological chaperone is 2-acetamido-1,2-dideoxynojirimycin.

8. The method of claim 1, wherein Alzheimer'"'"'s Disease is early onset familial Alzheimer'"'"'s Disease.

9. The method of claim 1, wherein Alzheimer'"'"'s Disease is caused by Down syndrome.

10. The method of claim 1, wherein the pharmacological chaperone is N-acetyl-glucosamine-thiazoline.

11. A method for the treatment of Alzheimer'"'"'s Disease in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone, wherein said pharmacological chaperone is 2-acetamido-1,2dideoxynojirimycin.

12. A method for the treatment of Alzheimer'"'"'s Disease in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone, wherein said pharmacological chaperone is N-acetyl-glucosamine-thiazoline.