Methods of treating a metabolic syndrome by modulating heat shock protein (HSP) 90-β

Patent metadata

Field	Value
Publication number	US-9533002-B2
Application number	US-201313902354-A
Country	US
Kind code	B2
Filing date	May 24, 2013
Priority date	May 25, 2012
Publication date	Jan 3, 2017
Grant date	Jan 3, 2017

Abstract

The invention provides methods of treatment of metabolic syndrome with HSP90 inhibitors, particularly HSP90β inhibitors. The invention provides methods of diagnosis and monitoring of metabolic syndrome using HSP90, particularly HSP90β, expression and activity level.

First claim

The invention claimed is:

1. A method of treating a metabolic syndrome in a subject, comprising administering to the subject an HSP90 inhibitor, wherein the subject with metabolic syndrome exhibits three or more of the following signs:
a) Blood pressure equal to or higher than 130/85 mmHg;
b) Fasting blood glucose equal to or higher than 100 mg/dL;
c) Large waist circumference wherein a large waist circumference is 40 inches or more for men and 35 inches or more for women;
d) Low HDL cholesterol wherein low HDL cholesterol is under 40 mg/dL for men and under 50 mg/dL for women; and
e) Triglycerides equal to or higher than 150 mg/dL,
thereby treating the metabolic syndrome in the subject, and wherein the HSP90 inhibitor comprises a nucleic acid molecule.

2. The method of claim 1 , wherein the HSP90 inhibitor is an inhibitor of HSP90β.

3. The method of claim 1 , wherein the HSP90 inhibitor is a specific inhibitor of HSP90β.

4. The method of claim 1 or 2 , wherein the HSP90 inhibitor is an inhibitor of HSP90α.

5. The method of claim 1 , wherein the metabolic syndrome comprises type 2 diabetes.

6. The method of claim 1 , wherein the metabolic syndrome comprises type 1 diabetes.

7. The method of claim 1 , wherein the metabolic syndrome comprises insulin resistance.

8. The method of claim 1 , wherein the metabolic syndrome comprises insulin insufficiency.

9. The method of claim 1 , wherein the metabolic syndrome comprises obesity.

10. The method of claim 1 , wherein the metabolic syndrome comprises hyperinsulinemia.

11. The method of claim 1 , wherein the metabolic syndrome comprises impaired glucose tolerance (IGT).

12. The method of claim 1 , wherein the nucleic acid inhibitor comprises an antisense nucleic acid molecule.

13. The method of claim 1 , wherein the nucleic acid inhibitor comprises a double stranded nucleic acid molecule.

14. The method of claim 13 , wherein the nucleic acid inhibitor comprises a double stranded RNA selected from the group consisting of an siRNA, a shRNA, and a dicer substrate siRNA (DsiRNA).

15. The method of claim 1 , wherein treating the metabolic syndrome comprises normalizing a blood glucose level in a subject.

16. The method of claim 1 , wherein treating the metabolic syndrome comprises normalizing an Hb1Ac level in a subject.

17. The method of claim 1 , wherein treating the metabolic syndrome comprises prevention of at least one complication of diabetes associated with poor circulation.

18. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one sign or symptom of type 2 diabetes.

19. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one sign or symptom of type 1 diabetes.

20. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one sign or symptom of insulin resistance.

21. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one sign or symptom of insulin insufficiency.

22. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one sign or symptom of hyperinsulinemia.

23. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one sign or symptom of impaired glucose tolerance (IGT).

24. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one sign or symptom of obesity.

25. The method of claim 1 , wherein treating the metabolic syndrome comprises amelioration of at least one of
a) Blood pressure equal to or higher than 130/85 mmHg;
b) Fasting blood glucose equal to or higher than 100 mg/dL;
c) Large waist circumference wherein a large waist circumference is 40 inches or more for men and 35 inches or more for women;
d) Low HDL cholesterol wherein low HDL cholesterol is under 40 mg/dL for men and under 50 mg/dL; and
e) Triglycerides equal to or higher than 150 mg/dL.

26. The method of claim 25 , wherein treating the metabolic syndrome comprises amelioration of elevated blood pressure equal to or higher than 130/85 mmHg.

27. The method of claim 25 , wherein treating the metabolic syndrome comprises amelioration of elevated fasting blood glucose equal to or higher than 100 mg/dL.

28. The method of claim 25 , wherein treating the metabolic syndrome comprises amelioration of large waist circumference wherein a large waist circumference is 40 inches or more for men and 35 inches or more for women.

29. The method of claim 25 , wherein treating the metabolic syndrome comprises amelioration of low HDL cholesterol by increasing HDL cholesterol wherein low HDL cholesterol is under 40 mg/dL for men and under 50 mg/dL.

30. The method of claim 25 , wherein treating the metabolic syndrome comprises amelioration of elevated triglycerides equal to or higher than 150 mg/dL.

31. The method of claim 1 , wherein treating metabolic syndrome comprises amelioration of fatty liver.

32. The method of claim 1 , wherein treating metabolic syndrome comprises modulation of fat deposition.

Assignees

• Narain Niven Rajin
• Sarangarajan Rangaprasad
• Vishnudas Vivek K
• Jing Enxuan
• Berg Llc

Inventors

• Narain Niven Rajin
• Sarangarajan Rangaprasad
• Vishnudas Vivek K
• Jing Enxuan

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K31/7056 Primary

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K31/366

  having six-membered rings, e.g. delta-lactones · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title