# US 10,441,574 B2 · Treatment for wolfram syndrome and other endoplasmic reticulum stress disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,574 B2 - Document ID: US10441574B2 - Status: Granted - Kind: B2 - Application number: 15/526,663 - Filed: 2015-11-13 - Published: 2018-08-02 - Granted: 2019-10-15 - Earliest claimed: 2014-11-13 - Assignees: Washington University - Applicants: Fumihiko Urano; Simin Lu - Inventors: Fumihiko Urano; Simin Lu - Web page: https://patentgrep.com/patent/US10441574B2 ## CPC - A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin - A61K 9/0019: {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)} - A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 25/00: Drugs for disorders of the nervous system - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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. ## Claims ### Claim 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. ### Claim 2 (depends on 1) 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. ### Claim 3 (depends on 1) 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. ### Claim 4 (depends on 1) The method of claim 1, wherein the ryanodine receptor inhibitor is administered in a composition further comprising a pharmaceutically acceptable carrier. ### Claim 5 (depends on 4) 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. ### Claim 6 (depends on 1) The method of claim 1, wherein the subject is a human. ### Claim 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. ### Claim 8 (depends on 7) The method of claim 7, wherein the composition comprises dantrolene sodium. ### Claim 9 (depends on 7) The method of claim 7, wherein the composition further comprises a pharmaceutically acceptable carrier. ### Claim 10 (depends on 8) 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. ### Claim 11 (depends on 8) 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. ### Claim 12 (depends on 7) The method of claim 7, further comprising administering at least one second active agent. ### Claim 13 (depends on 12) 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. ### Claim 14 (depends on 12) 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. ### Claim 15 (depends on 14) The method of claim 14, wherein the second active agent comprises pioglitazone. ### Claim 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. ### Claim 17 (depends on 16) The method of claim 16, wherein the dantrolene or a pharmaceutically acceptable salt or hydrate thereof comprises dantrolene sodium. ### Claim 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. ### Claim 19 (depends on 18) The method of claim 18, wherein the composition comprises dantrolene sodium. ### Claim 20 (depends on 19) 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.