Methods for the regulation of matrix metalloproteinase expression

Patent metadata

Field	Value
Publication number	US-11266709-B2
Application number	US-201916700321-A
Country	US
Kind code	B2
Filing date	Dec 2, 2019
Priority date	Jun 26, 2013
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

The disclosure provides methods of reducing MMP-9 expression and/or MMP-9 activity in a mammalian subject. The disclosure also provides methods of increasing TIMP-1 expression and/or TIMP-1 activity in a mammalian subject. The methods comprise administering a therapeutically effective amount of an aromatic-cationic peptide to a subject in need thereof.

First claim

What is claimed is:

1. A method for ameliorating a reduction in left ventricular fractional shortening (LVFS) in a mammalian subject in need thereof comprising administering the mammalian subject a therapeutically effective amount of D-Arg-2′6′-Dmt-Lys-Phe-NH 2 , or a pharmaceutically acceptable salt thereof, wherein the subject has suffered a myocardial infarction, wherein ameliorating a reduction in LVFS comprises reducing matrix metalloproteinase 9 (MMP-9) gene expression, and wherein ameliorating a reduction in LVFS comprises increasing tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expression.

2. The method of claim 1 , wherein the aromatic-cationic peptide is administered about 0.5 hours to about 4 hours after the myocardial infarction.

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

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

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

6. The method of claim 5 , 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, an α-receptor blocking drug, a sympathetic nerve inhibitor, a digitalis formulation, an inotrope, captopril, and an antihyperlipidemic drug.

7. A method for ameliorating a reduction in left ventricular stroke volume or left ventricular ejection fraction in a mammalian subject in need thereof comprising administering the mammalian subject a therapeutically effective amount of D-Arg-2′6′-Dmt-Lys-Phe-NH 2 , or a pharmaceutically acceptable salt thereof, wherein the subject has suffered a myocardial infarction, wherein ameliorating a reduction in left ventricular stroke volume or left ventricular ejection fraction comprises reducing matrix metalloproteinase 9 (MMP-9) gene expression, and wherein ameliorating a reduction in left ventricular stroke volume or left ventricular ejection fraction comprises increasing tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expression.

8. The method of claim 7 , wherein the aromatic-cationic peptide is administered about 0.5 hours to about 4 hours after the myocardial infarction.

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

10. The method of claim 7 , wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.

11. The method of claim 7 , 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, an α-receptor blocking drug, a sympathetic nerve inhibitor, a digitalis formulation, an inotrope, captopril, and an antihyperlipidemic drug.

Assignees

• Stealth Biotherapeutics Corp
• Stealth Biotherapeutics Inc

Inventors

• Wilson D Travis
• Kloner Robert A

Classifications

• A61K31/401

  Proline; Derivatives thereof, e.g. captopril · CPC title

• A61K38/55

  Protease inhibitors · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K38/07 Primary

  Tetrapeptides · CPC title