PDE5 inhibitor compositions and methods for treating cardiac indications

• US 8,299,083 B2
• Filed: 08/17/2005
• Issued: 10/30/2012
• Est. Priority Date: 08/17/2004
• Status: Active Grant

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Kass, David, Takimoto, Eiki, Champion, Hunter
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US11/660,440
• Publication Number:
  US 20090062313A1
• Time in Patent Office: 2,631 Days
• Field of Search: 514/263.1, 514/250
• US Class Current: 514/263.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• 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: A61P 9/12 Antihypertensives

Abstract

The invention features methods and compositions featuring a PDE5 inhibitor for treating or preventing a cardiac indication in a subject.

Claims

1. A method of enhancing cardiac function in a subject having left ventricular hypertrophy, the method comprising administering to the subject an effective amount of a PDE5 inhibitor, wherein the administration of the inhibitor enhances cardiac function.

2. The method of claim 1, wherein the method reduces or reverses cardiac chamber remodeling.

3. The method of claim 2, wherein the method reduces or reverses cardiac dilation.

4. The method of claim 1, wherein the method reduces or reverses cardiac muscle cell remodeling.

5. The method of claim 4, wherein the method reduces myocyte hypertrophy.

6. The method of claim 1, wherein the method reduces or reverses molecular remodeling.

7. The method of claim 6, wherein the PDE5 inhibitor reduces expression of an agent selected from the group consisting of metalloproteinases, calcineurin, mitogen activated kinase, Akt kinase, nuclear factor of activated T-cells (NFAT), RhoA and Rho kinase, PI3 kinase, components of a gp130/Stat-3 pathway, nitrotyrosine, nitric oxide synthase, an agent associated with nitric oxide synthase uncoupling, and an agent associated with oxidative stress.

8. The method of claim 6, wherein the PDE5 inhibitor reduces the biological activity of an agent selected from the group consisting of metalloproteinases, calcineurin, mitogen activated kinase, Akt kinase, NFAT, Rho A and Rho kinase, PI3 kinase, components of the gp130/Stat-3 pathway, nitrotyrosine, nitric oxide synthase, an agent associated with nitric oxide synthase uncoupling and an agent associated with oxidative stress.

9. The method of claim 1, wherein the PDE5 inhibitor enhances cGMP-dependent signaling via Protein Kinase G.

10. The method of claim 1, wherein the cardiac chamber, cellular or molecular remodeling is induced by a stimulus.

11. A method of reducing left ventricular hypertrophy in a subject having left ventricular hypertrophy, the method comprising administering to the subject an effective amount of a PDE5 inhibitor, wherein the administration of the inhibitor reduces cardiac hypertrophy.

12. The method of claim 11, wherein the method reverses cardiac hypertrophy.

13. A method of reversing left ventricular cardiac hypertrophy in a subject, the method comprising administering to a subject identified as having left ventricular cardiac hypertrophy an effective amount of a PDE5 inhibitor, wherein the administration of the inhibitor reverses left ventricular cardiac hypertrophy.