Treatment for wolfram syndrome and other endoplasmic reticulum stress disorders

Patent metadata

Field	Value
Publication number	US-10441574-B2
Application number	US-201515526663-A
Country	US
Kind code	B2
Filing date	Nov 13, 2015
Priority date	Nov 13, 2014
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

The present invention generally relates to a method of treating or preventing an endoplasmic reticulum stress disorder in subjects, such as a method of treating or preventing Wolfram syndrome.

First claim

What is claimed is:

1. A method of treating Wolfram Syndrome in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a ryanodine receptor inhibitor, wherein the ryanodine receptor inhibitor comprises azumolene or a pharmaceutically acceptable salt or hydrate thereof.

2. The method of claim 1 , wherein the ryanodine receptor inhibitor is administered intravenously in an amount of from about 0.05 mg to about 30 mg per kg of body weight.

3. The method of claim 1 , wherein the ryanodine receptor inhibitor is administered orally in an amount of from about 0.1 mg to about 75 mg per kg of bodyweight.

4. The method of claim 1 , wherein the ryanodine receptor inhibitor is administered in a composition further comprising a pharmaceutically acceptable carrier.

5. The method of claim 4 , wherein the composition further comprises at least one second active agent, wherein the second active agent modulates the transport of calcium (Ca2+) ions to and/or from the endoplasmic reticulum in a cell.

6. The method of claim 1 , wherein the subject is a human.

7. A method of treating Wolfram Syndrome in a human subject in need thereof comprising administering to the subject a therapeutically effective amount of a composition comprising dantrolene or a pharmaceutically acceptable salt or hydrate thereof, wherein the human subject has an age that is 16 years or less.

8. The method of claim 7 , wherein the composition comprises dantrolene sodium.

9. The method of claim 7 , wherein the composition further comprises a pharmaceutically acceptable carrier.

10. The method of claim 8 , wherein the dantrolene sodium is administered intravenously in an amount of from about 0.05 mg to about 30 mg per kg of body weight.

11. The method of claim 8 , wherein the dantrolene sodium is administered orally in an amount of from about 0.1 mg to about 75 mg per kg of bodyweight.

12. The method of claim 7 , further comprising administering at least one second active agent.

13. The method of claim 12 , wherein the second active agent modulates the transport of calcium (Ca2+) ions to and/or from the endoplasmic reticulum in a cell.

14. The method of claim 12 , wherein the second active agent comprises a compound that enhances the activity of sarco/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pumps.

15. The method of claim 14 , wherein the second active agent comprises pioglitazone.

16. A method of treating Wolfram Syndrome in a human subject in need thereof consisting of administering to the subject a therapeutically effective amount of a composition consisting of dantrolene or a pharmaceutically acceptable salt or hydrate thereof and one or more pharmaceutically acceptable carriers.

17. The method of claim 16 , wherein the dantrolene or a pharmaceutically acceptable salt or hydrate thereof comprises dantrolene sodium.

18. A method of treating Wolfram Syndrome in a human subject in need thereof comprising administering to the subject a therapeutically effective amount of a composition comprising dantrolene or a pharmaceutically acceptable salt or hydrate thereof, wherein the subject does not have Type 1 or Type 2 diabetes.

19. The method of claim 18 , wherein the composition comprises dantrolene sodium.

20. The method of claim 19 , wherein the dantrolene sodium is administered intravenously in an amount of from about 0.05 mg to about 30 mg per kg of body weight or orally in an amount of from about 0.1 mg to about 75 mg per kg of bodyweight.

Assignees

• Urano Fumihiko
• Lu Simin
• Univ Washington

Inventors

• Urano Fumihiko
• Lu Simin

Classifications

• A61K38/177

  Receptors; Cell surface antigens; Cell surface determinants · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K31/4178 Primary

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title