IL1RL-1 as a cardiovascular disease marker and therapeutic target

• US 7,670,769 B2
• Filed: 05/09/2003
• Issued: 03/02/2010
• Est. Priority Date: 05/09/2002
• 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): STANFIELD, CHERIE MICHELLE
• Application Number:
  US10/435,482
• Publication Number:
  US 20040048286A1
• Time in Patent Office: 2,489 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: A61K 39/00112 Receptors for interferons [IFN]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• 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 2800/324 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 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

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 for predicting outcome of a cardiovascular condition, comprising:

obtaining a level of an IL1RL-1 molecule in a subject having or suspected of having a cardiovascular condition by contacting a biological sample from the subject with an agent, wherein the agent specifically binds to the IL1RL-1molecule, and

comparing the level of the IL1RL-1 molecule to a predetermined value specific for predicting outcome of the cardiovascular condition, wherein the level of the IL1RL-1 molecule in comparison to the predetermined value is indicative of the outcome of the cardiovascular condition, and wherein an increased level in comparison to the predetermined value is indicative of a negative outcome and a decreased level is indicative of a positive outcome.

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

3. The method of claim 1, wherein the negative outcome is an increased risk of death and/or congestive heart failure (CHF).

4. The method of claim 3, wherein the increased risk of death is in-hospital death or death within 30 days.

5. The method of claim 1, wherein the level of the IL1RL-1 molecule is determined within 12 hours of an episode of ischemic discomfort or 1, 3, 12 or 24 hours thereafter.

6. The method of claim 5, wherein the level of the IL1RL-1 molecule is determined within 6 hours of an episode of ischemic discomfort or 1, 3, 12 or 24 hours thereafter.

7. The method of claim 1, wherein the method further comprises measuring at least one other marker related to the cardiovascular condition.

8. The method of claim 7, wherein the at least one other marker is a circulating catecholamine, angiotensin II, creatinine, creatine kinase MB isoenzyme (CK-MB), C-reactive protein (CRP), a troponin, a natriuretic peptide or a marker of oxidative stress.

9. The method of claim 8, wherein the at least one other marker is a troponin and brain natriuretic peptide (BNP).

10. The method of claim 8 or 9, wherein the troponin is cardiac troponin I.

11. The method of claim 8, wherein the circulating catecholamine is norepinephrine, dopamine or epinephrine.

12. The method of claim 8, wherein the natriuretic peptide is brain natriuretic peptide (BNP) or pro-atrial natriuretic peptide (ProANP).

13. The method of claim 11, wherein the natriuretic peptide is brain natriuretic peptide (BNP).

14. The method of claim 8, wherein the marker of oxidative stress is adrenolutin or malondialdehyde.

15. The method of claim 1, wherein the level of the IL1RL-1 molecule is obtained from a biopsy sample or a biological fluid sample.

16. The method of claim 15, wherein the biological fluid sample is a blood or serum sample.

17. The method of claim 1, wherein the subject is without ischemic disease.

18. The method of claim 1, wherein the subject has received or is receiving treatment for a cardiovascular condition.

19. The method of claim 18, wherein the cardiovascular condition is myocardial infarction or heart failure.

38. The method of claim 1, wherein the IL1RL-1 molecule is soluble IL1RL-1.

40. The method of claim 1, wherein the level of the IL1RL-1 molecule is determined with nucleic acid hybridization or an antibody-based detection method.

20. A method for predicting outcome of a cardiovascular condition, comprising:

obtaining a first level of an IL1RL-1 molecule in a subject having or suspected of having a cardiovascular condition by contacting a first biological sample from the subject with a first agent, wherein the first agent specificaly binds to the IL1RL-1 molecule,

obtaining a second level of the IL1RL-1 molecule in the subject having or suspected of having a cardiovascular condition by contacting a second biological sample from the subject with a second agent, wherein the second agent specifically binds to the IL1RL-1 molecule, and

comparing the change in the levels of the IL1RL-1 molecule to a predetermined value specific for predicting outcome of the cardiovascular condition, wherein the change in the levels of the IL1RL-1 molecule in comparison to the predetermined value is indicative of the outcome of the cardiovascular condition.

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

22. The method of claim 20, wherein the first level is obtained within 24 hours of a myocardial infarction.

23. The method of claim 20 or 22, wherein the second level is obtained 2 weeks after the first level.

24. The method of claim 20, wherein the change in the levels of the IL1RL-1 molecule in comparison to the predetermined value is indicative of an increased risk of death or transplantation.

25. The method of claim 20, wherein the method further comprises measuring at least one other marker related to the cardiovascular condition.

26. The method of claim 25, wherein the at least one other marker is a circulating catecholamine, angiotensin II, creatinine, creatine kinase MB isoenzyme (CK-MB), C-reactive protein (CRP), a troponin, a natriuretic peptide or a marker of oxidative stress.

27. The method of claim 26, wherein the at least one other marker is a troponin and brain natriuretic peptide (BNP).

28. The method of claim 26 or 27, wherein the troponin is cardiac troponin I.

29. The method of claim 26, wherein the circulating catecholamine is norepinepbrine, dopamine or epinephrine.

30. The method of claim 26, wherein the natriuretic peptide is brain natriuretic peptide (BNP) or pro-atrial natriuretic peptide (ProANP).

31. The method of claim 30, wherein the natriuretic peptide is brain natriuretic peptide (BNP).

32. The method of claim 26, wherein the marker of oxidative stress is adrenolutin or malondialdehyde.

33. The method of claim 20, wherein the levels of the IL1RL-1 molecule are obtained from biopsy samples or biological fluid sample.

34. The method of claim 33, wherein the biological fluid samples are blood or serum sample.

35. The method of claim 20, wherein the subject is without ischemic disease.

36. The method of claim 20, wherein the subject has received or is receiving treatment for a cardiovascular condition.

37. The method of claim 36, wherein the cardiovascular condition is myocardial infarction or heart failure.

39. The method of claim 20, wherein the IL1RL-1 molecule is soluble IL1RL-1.

41. The method of claim 20, wherein the first level and second level of the IL1RL-1 molecule are each determined wit nucleic acid hybridization or an antibody-based detection method.

42. The method of claim 20, wherein the first agent and second agent are the same type of agent.