Method for Treating Cerebral Amyloid Angiopathy Using Pharmacological Chaperones to Increase the Activity of Gangliosidases

• US 20150374733A1
• Filed: 05/05/2015
• Published: 12/31/2015
• Est. Priority Date: 10/19/2009
• Status: Active Grant

• Current Assignee: Amicus Therapeutics, Inc.
• Original Assignee: Amicus Therapeutics, Inc.
• Inventors: Wustman, Brandon Alan, Valenzano, Kenneth, Boyd, Robert
• Granted Patent: US 9,931,353 B2
• Time in Patent Office: 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 Cerebral Amyloid Angiopathy 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 Cerebral Amyloid Angiopathy in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone.

2. The method of claim 1, wherein the pharmacological chaperone increases production of sAPPα

.

3. The method of claim 1, wherein the pharmacological chaperone reversibly binds to a gangliosidase.

4. The method of claim 3, wherein the gangliosidase is selected from the group consisting of:

β

-hexosaminidase A, β

-hexosaminidase B, and β

-hexosaminidase S.

5. The method of claim 4, wherein the gangliosidase is β

-hexosaminidase A.

6. The method of claim 1, wherein the pharmacological chaperone increases trafficking of a 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.

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

8. The method of claim 1, wherein the pharmacological chaperone is selected from 2-acetamido-1,2-dideoxynojirimycin and N-acetyl-glucosamine-thiazoline.

9. The method of claim 8, wherein the pharmacological chaperone increases production of sAPPα

.

10. The method of claim 8, wherein the pharmacological chaperone is 2-acetamido-1,2-dideoxynojirimycin.

11. The method of claim 8, wherein the pharmacological chaperone is N-acetyl-glucosamine-thiazoline.

12. The method of claim 1, wherein the Cerebral Amyloid Angiopathy is Familial Cerebral Amyloid Angiopathy.

13. The method of claim 12, wherein the Familial Cerebral Amyloid Angiopathy is caused by a mutation in amyloid precursor protein (APP).

14. A method for the treatment of Cerebral Amyloid Angiopathy in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone that reversibly binds to a gangliosidase is selected from the group consisting of:

β

-hexosaminidase A, β

-hexosaminidase B, and β

-hexosaminidase S.

15. The method of claim 14, wherein the pharmacological chaperone increases production of sAPPα

.

16. The method of claim 14, wherein the gangliosidase is β

-hexosaminidase A.

17. The method of claim 14, wherein the pharmacological chaperone increases trafficking of the gangliosidase from the endoplasmic reticulum into the lysosome.

18. The method of claim 14, wherein the pharmacological chaperone increases mutant and/or wild-type activity of the gangliosidase.

19. The method of claim 14, wherein the pharmacological chaperone is selected from 2-acetamido-1,2-dideoxynojirimycin and N-acetyl-glucosamine-thiazoline.

20. The method of claim 14, wherein the Cerebral Amyloid Angiopathy is Familial Cerebral Amyloid Angiopathy.