IP Library Granted Patent US 9,428,753
Granted Patent B2
US 9,428,753 · App. 14/178,384 · Granted Aug 30, 2016

Use of LXR antagonists for treatment of side effects of elevated glucocorticoid levels

Inventors: Carolyn Cummins (Toronto, CA); Arturo Orellana (Toronto, CA); Rucha Patel (Toronto, CA); Fernando A. Fernandez (Toronto, CA)
Assignees: THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO; Fernando A. Fernandez; Arturo Orellana
C12N15/1138A61K31/18A61K31/341A61K31/573C07J41/0061
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Quick Facts
Patent No.
US 9,428,753
App. No.
14/178,384
Granted
Aug 30, 2016
Kind
B2
Abstract

The present application is directed to uses of an agent that antagonizes the LXRβ receptor for the treatment of side effects associated with elevated glucocorticoid levels as well as uses of a glucocorticoid in combination with the agent that antagonizes the LXRβ receptor for treatment of a disease wherein glucocorticoid treatment is indicated.

Claims (24)

1. A method of treating a side effect of elevated glucocorticoid levels comprising administering a therapeutically effective amount of an agent that antagonizes the LXRβ receptor to a subject in need thereof, wherein the agent that antagonizes the LXRβ receptor is GSK2033, or a pharmaceutically acceptable solvates thereof.

2. The method of claim 1 , wherein the side effect of elevated glucocorticoid levels is selected from one or more of insulin resistance, hyperglycemia, diabetes, fatty liver , hypertension, bone loss, muscle wasting, muscle weakness, increased appetite, weight gain, deposits of fat in the chest, face, upper back or stomach, water retention or salt retention leading to swelling or edema, high blood pressure, black and blue marks, cataracts, acne, thinning of the skin, stomach ulcers, increased sweating, mood swings, adrenal suppression, adrenal crisis, and psychological problems.

3. The method of claim 2 , wherein the side effect of elevated glucocorticoid levels is a gluconeogenic side effect.

4. The method of claim 1 , wherein the elevated glucocorticoid levels are the result of elevated endogenous glucocorticoid levels.

5. The method of claim 4 , wherein the endogenous glucocorticoid levels are elevated because of the presence of a condition, disease or disorder selected from Cushing's syndrome, type 2 diabetes and chronic stress.

6. The method of claim 1 , wherein the elevated glueoeorticoid levels are the results of administration of exogenous glucocorticoid.

7. The method of claim 6 , wherein the glucocorticoid is selected from dexamethasone, betamethasone, cortisone, prednisone, prednisolone, methylprednisolone, beclometasone, fludrocortisone, deoxycorticosterone acetate, triamcinolone, and cortisol (hydrocortisone) and pharmaceutically acceptable salts, ester and amide prodrugs and solvates thereof.

8. The method of claim 7 , wherein the glucocorticoid is dexamethasone.

9. A method of treating a side effect of elevated glucocorticoid levels comprising administering a therapeutically effective amount of an agent that antagonizes the LXRβ receptor to a subject in need thereof, wherein the agent that antagonizes the LXRβ receptor is Amgen54 or a pharmaceutically acceptable solvate thereof.

10. The method of claim 9 , wherein the side effect of elevated glucocorticoid levels is selected from one or more of insulin resistance, hyperglycemia, diabetes, fatty liver, hypertension, bone loss, muscle wasting, muscle weakness, increased appetite, weight gain, deposits of fat in the chest, face, upper back or stomach, water retention or salt retention leading to swelling or edema, high blood pressure, black and blue marks, cataracts, acne, thinning of the skin, stomach ulcers, increased sweating, mood swings, adrenal suppression adrenal crisis, and psychological problems.

11. The method of claim 10 , wherein the side effect of elevated glucocorticoid levels is a gluconeogenic side effect.

12. The method of claim 9 , wherein the elevated glucocorticoid levels are the result of elevated endogenous glucocorticoid levels.

13. The method of claim 12 , wherein the endogenous glucocorticoid levels are elevated because of the presence of a condition, disease or disorder selected from Cushing's syndrome, type 2 diabetes and chronic stress.

14. The method of claim 9 , wherein the elevated glucocorticoid levels are the results of administration of exogenous glucocorticoid.

15. The method of claim 14 , wherein the glucocorticoid is selected from dexamethasone, betamethasone, cortisone, prednisone, prednisolone, methylprednisolone, beclometasone, fludrocortisone, deoxycorticosterone acetate, triamcinolone, and cortisol (hydrocortisone) and pharmaceutically acceptable salts, ester and amide prodrugs and solvates thereof.

16. The method of claim 15 , wherein the glucocorticoid is dexamethasone.

17. A method of treating a side effect of elevated glucocorticoid levels comprising administering a therapeutically effective amount of an agent that antagonizes the LXRβ receptor to a subject in need thereof, wherein the agent that antagonizes the LXRβ receptor is DMHCI OR a pharmaceutically acceptable solvate thereof.

18. The method of claim 17 , wherein the side effect of elevated glucocorticoid levels is selected from one or more of insulin resistance, hyperglycemia, diabetes, fatty liver, hypertension, bone loss, muscle wasting, muscle weakness, increased appetite, weight gain, deposits of fat in the chest, face, upper back or stomach, water retention or salt retention leading to swelling or edema, high blood pressure, black and blue marks, cataracts, acne, thinning of the skin, stomach ulcers, increased sweating, mood swings, adrenal suppression, adrenal crisis, and psychological problems.

19. The method of claim 18 , wherein the side effect of elevated glucocorticoid levels is a gluconeogenie side effect.

20. The method of claim 17 , wherein the elevated glucocorticoid levels are the result of elevated endogenous glucocorticoid levels.

21. The method of claim 20 , wherein the endogenous glucocorticoid levels are elevated because of the presence of a condition, disease or disorder selected from Cushing's syndrome, type 2 diabetes and chronic stress.

22. The method of claim 17 , wherein the elevated glucocorticoid levels are the results of administration of exogenous glucocorticoid.

23. The method of claim 22 , wherein the glucocorticoid is selected from dexamethasone, betamethasone, cortisone, prednisone, prednisolone, methylprednisolone, beclometasone, fludrocortisone, deoxycorticosterone acetate, triamcinolone, and cortisol (hydrocortisone) and pharmaceutically acceptable salts, ester and amide prodrugs and solvates thereof.

24. The method of claim 23 , wherein the glucocorticoid is dexamethasone.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 13, 2014
From: CUMMINS, CAROLYN; PATEL, RUCHA
To: THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO
Reel/Frame 032210/0792 →
Priority Claims (1)
CA 2819448 · Jun 21, 2013 · national
Continuity (2)
Provisional Application 61792502 · Mar 15, 2013
Related Publication 20140271673A1 · Sep 18, 2014