Methods for treatment of cardiovascular disease

• US 8,871,452 B2
• Filed: 03/07/2013
• Issued: 10/28/2014
• Est. Priority Date: 11/09/2000
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Lee, Richard T.
• Primary Examiner(s): Landsman, Robert
• Assistant Examiner(s): Hissong, Bruce D
• Application Number:
  US13/788,922
• Publication Number:
  US 20130317030A1
• Time in Patent Office: 600 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/2871 Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/323 Arteriosclerosis, Stenosis
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5023 on expression patterns
• CPC Class Codes: G01N 33/5041 involving analysis of members of signalling pathways
• CPC Class Codes: G01N 33/5061 Muscle cells
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

This invention pertains to methods and compositions for the diagnosis and treatment of cardiovascular conditions. More specifically, the invention relates to isolated molecules that can be used to diagnose and/or treat cardiovascular conditions including cardiac hypertrophy, myocardial infarction, stroke, arteriosclerosis, and heart failure.

Claims

1. A method of treating a subject having a cardiovascular condition, said method comprising:

performing an assay to determine a level of soluble Interleukin-1 Receptor-Like-1 (ST2) in a biological sample from a subject having a cardiovascular condition;

comparing the level of soluble ST2 in the biological sample to a predetermined value;

identifying a subject having an elevated level of soluble ST2 as compared to the predetermined value; and

administering to the identified subject a treatment comprising a therapeutically effective amount of a renin-angiotensin system inhibitor and a therapeutically effective amount of a beta-adrenergic receptor blocker.

2. The method of claim 1, wherein the cardiovascular condition is selected from the group consisting of cardiac hypertrophy, myocardial infarction, stroke, and heart failure.

3. The method of claim 1, wherein the sample comprises a biological fluid.

4. The method of claim 3, wherein the biological fluid is blood or serum.

5. The method of claim 1, wherein the assay comprises contacting the biological sample with an antibody that specifically binds to soluble ST2.

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

7. The method of claim 1, wherein the renin-angiotensin system inhibitor is selected from the group consisting of:

an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), an angiotensin II receptor antagonist, an agent that activates the catabolism of angiotensin II, and an agent that prevents the synthesis of angiotensin I.

8. The method of claim 1, wherein the beta-adrenergic receptor blocker is selected from the group consisting of:

atenolol, acebutolol, alprenolol, befunolol, betaxolol, bunitrolol, carteolol, celiprolol, hedroxalol, indenolol, labetalol, levobunolol, mepindolol, methypranol, metindol, metoprolol, metrizoranolol, oxprenolol, pindolol, propranolol, practolol, sotalol, nadolol, tiprenolol, tomalolol, timolol, bupranolol, penbutolol, and trimepranol.

9. The method of claim 1, wherein the predetermined value is a level of secreted ST2 in a healthy subject.

10. The method of claim 1, wherein the treatment is administered orally, nasally, intradermally, by infusion, intravenously, or intramuscularly.

11. A method of treating a subject having a cardiovascular condition, said method comprising:

performing an assay to determine a level of soluble Interleukin-1 Receptor-Like-1 (ST2) in a biological sample from a subject having a cardiovascular condition;

comparing the level of soluble ST2 in the biological sample to a predetermined value;

identifying a subject having an elevated level of soluble ST2 as compared to the predetermined value; and

administering to the identified subject a treatment comprising a therapeutically effective amount of a renin-angiotensin system inhibitor.

12. The method of claim 11, wherein the cardiovascular condition is selected from the group consisting of cardiac hypertrophy, myocardial infarction, stroke, and heart failure.

13. The method of claim 11, wherein the sample comprises a biological fluid.

14. The method of claim 13, wherein the biological fluid is blood or serum.

15. The method of claim 11, wherein the assay comprises contacting the biological sample with an antibody that specifically binds to soluble ST2.

16. The method of claim 11, wherein the subject is a human.

17. The method of claim 11, wherein the renin-angiotensin system inhibitor is selected from the group consisting of:

an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), an angiotensin II receptor antagonist, an agent that activates the catabolism of angiotensin II, and an agent that prevents the synthesis of angiotensin I.

18. The method of claim 11, wherein the predetermined value is a level of secreted ST2 in a healthy subject.

19. The method of claim 11, wherein the treatment is administered orally, nasally, intradermally, by infusion, intravenously, or intramuscularly.

20. A method of treating a subject having a cardiovascular condition, said method comprising:

performing an assay to determine a level of soluble Interleukin-1 Receptor-Like-1 (ST2) in a biological sample from a subject having a cardiovascular condition;

comparing the level of soluble ST2 in the biological sample to a predetermined value;

identifying a subject having an elevated level of soluble ST2 as compared to the predetermined value; and

administering to the identified subject a treatment comprising a therapeutically effective amount of a beta-adrenergic receptor blocker.

21. The method of claim 20, wherein the cardiovascular condition is selected from the group consisting of cardiac hypertrophy, myocardial infarction, stroke, and heart failure.

22. The method of claim 20, wherein the sample comprises a biological fluid.

23. The method of claim 22, wherein the biological fluid is blood or serum.

24. The method of claim 20, wherein the assay comprises contacting the biological sample with an antibody that specifically binds to soluble ST2.

25. The method of claim 20, wherein the subject is a human.

26. The method of claim 20, wherein the beta-adrenergic receptor blocker is selected from the group consisting of:

atenolol, acebutolol, alprenolol, befunolol, betaxolol, bunitrolol, carteolol, celiprolol, hedroxalol, indenolol, labetalol, levobunolol, mepindolol, methypranol, metindol, metoprolol, metrizoranolol, oxprenolol, pindolol, propranolol, practolol, sotalol, nadolol, tiprenolol, tomalolol, timolol, bupranolol, penbutolol, and trimepranol.

27. The method of claim 20, wherein the predetermined value is a level of secreted ST2 in a healthy subject.

28. The method of claim 20, wherein the treatment is administered orally, nasally, intradermally, by infusion, intravenously, or intramuscularly.