Methods for the prevention or treatment of no-reflow following ischemia/reperfusion injury

• US 9,345,738 B2
• Filed: 07/08/2011
• Issued: 05/24/2016
• Est. Priority Date: 07/09/2010
• Status: Active Grant

• Current Assignee: Stealth BioTherapeutics, Inc. (Morningside Group Ltd.)
• Original Assignee: Heart Institute Good Samaritan Hospital, Stealth BioTherapeutics Corp. (Morningside Group Ltd.)
• Inventors: Wilson, D. Travis, Borow, Kenneth, Kloner, Robert A., Hale, Sharon
• Primary Examiner(s): Ha, Julie
• Assistant Examiner(s): Hellman, Kristina M
• Application Number:
  US13/808,027
• Publication Number:
  US 20130196921A1
• Time in Patent Office: 1,782 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention provides methods of preventing or treating cardiac ischemia-reperfusion injury in a mammalian subject. The methods provide administering aromatic-cationic peptides in effective amounts to prevent or treat an anatomic zone of no re-flow in mammalian subjects. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof.

Claims

1. A method for treating a anatomic zone of no re-flow in a mammalian subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide D-Arg-2′

,6′

-Dmt-Lys-Phe-NH₂ or a pharmaceutically acceptable salt thereof, thereby treating the anatomical zone of no re-flow in the subject, wherein the anatomic zone of no re-flow comprises a zone of persistent ischemia.

2. The method of claim 1, further comprising the step of performing a revascularization procedure on the subject.

3. The method of claim 1, wherein the anatomic zone of no re-flow comprises a disruption of the microvasculature of the subject.

4. The method of claim 1, wherein the subject is suffering from an anatomic zone of no re-flow associated with a tissue selected from the group consisting of cardiovascular tissue, skeletal muscle tissue, cerebral tissue, and renal tissue.

5. The method of claim 2, wherein the subject is administered the peptide prior to the revascularization procedure, after the revascularization procedure, during and after the revascularization procedure, or continuously before, during, and after the revascularization procedure.

6. The method of claim 5, wherein the subject is administered the peptide for at least 3 hours after the revascularization procedure, for at least 5 hours after the revascularization procedure, for at least 8 hours after the revascularization procedure, for at least 12 hours after the revascularization procedure, or for at least 24 hours after the revascularization procedure.

7. The method of claim 5, wherein the subject is administered the peptide starting at least 8 hours before the revascularization procedure, starting at least 4 hours before the revascularization procedure, starting at least 2 hours before the revascularization procedure, starting at least 1 hour before the revascularization procedure, or starting at least 10 minutes before the revascularization procedure.

8. The method of claim 1, wherein the subject is suffering from a myocardial infarction or a stroke, or is in need of angioplasty.

9. The method of claim 2, wherein the revascularization procedure is selected from the group consisting of balloon angioplasty, insertion of a bypass graft, insertion of a stent, percutaneous transluminal coronary angioplasty, or directional coronary atherectomy.

10. The method of claim 2, wherein the revascularization procedure is removal of an occlusion.

11. The method of claim 2, wherein the revascularization procedure is administration of one or more thrombolytic agents.

12. The method of claim 11, wherein the one or more thrombolytic agents are selected from the group consisting of tissue plasminogen activator, urokinase, prourokinase, streptokinase, acylated form of plasminogen, acylated form of plasmin, and acylated streptokinase-plasminogen complex.