METHODS FOR THE PREVENTION OR TREATMENT OF HEART FAILURE

• US 20110082084A1
• Filed: 10/04/2010
• Published: 04/07/2011
• Est. Priority Date: 10/05/2009
• Status: Abandoned Application

• Current Assignee: Cornell University, University of Washington
• Original Assignee: University of Washington
• Inventors: Rabinovitch, Peter S., Dai, Dao-Fu, Szeto, Hazel H.
• Application Number:
  US12/897,325
• Publication Number:
  US 20110082084A1
• Time in Patent Office: Days
• US Class Current: 514/15.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 5/0817 the first amino acid being Arg
• CPC Class Codes: C07K 5/1016 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic

Abstract

The disclosure provides methods of preventing or treating heart failure in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof.

Claims

1. A method of treating heart failure or hypertensive cardiomyopathy in a mammalian subject, comprising administering to the mammalian subject in need thereof a therapeutically effective amount of the peptide D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂ or Phe-D-Arg-Phe-Lys-NH_2.

2. The method of claim 1, wherein the peptide is D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂.

3. The method of claim 1, wherein the peptide is Phe-D-Arg-Phe-Lys-NH₂.

4. The method of claim 1, wherein the subject is suffering from heart failure.

5. The method of claim 4, wherein the heart failure results from hypertension;

ischemic heart disease;

exposure to a cardiotoxic compound;

myocarditis;

thyroid disease;

viral infection;

gingivitis;

drug abuse;

alcohol abuse;

pericarditis;

atherosclerosis;

vascular disease;

hypertrophic cardiomyopathy;

acute myocardial infarction;

left ventricular systolic dysfunction;

coronary bypass surgery;

starvation;

an eating disorder;

or a genetic defect.

6. The method of claim 1, wherein the subject is suffering hypertensive cardiomyopathy.

7. The method of claim 1, wherein myocardial contractility and cardiac output in the subject administered the peptide are increased compared to a control subject not administered the peptide.

8. The method of claim 7, wherein the myocardial contractility and cardiac output in the subject are increased at least 10% compared to a control subject not administered the peptide.

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

10. The method of claim 1, wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.

11. The method of claim 1, further comprising separately, sequentially or simultaneously administering a cardiovascular agent to the subject.

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

an anti-arrhthymia agent, a vasodilator, an anti-anginal agent, a corticosteroid, a cardioglycoside, a diuretic, a sedative, an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II antagonist, a thrombolytic agent, a calcium channel blocker, a throboxane receptor antagonist, a radical scavenger, an anti-platelet drug, a β

-adrenaline receptor blocking drug, α

-receptor blocking drug, a sympathetic nerve inhibitor, a digitalis formulation, an inotrope, and an antihyperlipidemic drug.

13. A method for increasing myocardial contractility and cardiac output in a subject suffering from heart failure or hypertensive cardiomyopathy comprising administering to the subject a therapeutically effective amount of the peptide D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂ or Phe-D-Arg-Phe-Lys-NH₂.