Methods for treatment of cardiovascular disease

• US 8,530,173 B2
• Filed: 06/01/2011
• Issued: 09/10/2013
• 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:
  US13/151,012
• Publication Number:
  US 20110280887A1
• Time in Patent Office: 832 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 for treating a subject to reduce the risk of developing a cardiovascular condition, the method comprising:

determining a level of secreted ST2 in a biological sample from a subject at risk of developing a cardiovascular condition;

comparing the level of secreted ST2 in the biological sample to a control;

identifying the subject having an elevated level of secreted ST2 relative to a control; and

administering to the identified subject an agent that reduces the risk of the cardiovascular condition.

2. The method of claim 1, wherein the cardiovascular condition is characterized by mechanical strain, mechanical overload, or mechanically-induced deformation in cardiac cells or tissue.

3. 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.

4. The method of claim 1, wherein the biological sample is blood or serum.

5. The method of claim 1, wherein the determining is performed using an antibody or an antibody fragment that binds to secreted ST2.

6. The method of claim 5, wherein the antibody or antibody fragment is labeled with a radioactive label or an enzyme.

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

8. The method of claim 1, wherein the control is a predetermined level.

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

10. The method of claim 1, wherein the subject is hypercholesterolemic, hypertriglyceridemic, hyperlidemic, a smoker, or hypertensive.

11. The method of claim 1, wherein the agent is selected from the group consisting of:

an anti-inflammatory agent, an anti-thrombotic agent, an anti-platelet agent, a fibrinolytic agent, a lipid-reducing agent, a direct thrombin inhibitor, a glycoprotein IIb/IIIa receptor inhibitor, a calcium channel blocker, a beta-adrenergic receptor blocker, a cyclooxygenase-2 inhibitor, and renin-angiotensin system (RAS) inhibitors.

12. 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.

13. The method of claim 1, wherein the agent is administered orally, rectally, topically, nasally, intradermally, transdermally, by infusion, intravenously, or intramuscularly.

14. The method of claim 1, wherein the agent is formulated for timed-release, delayed-release, or sustained-release.