Aromatic-cationic peptides and methods for using same

• US 9,988,422 B2
• Filed: 09/28/2012
• Issued: 06/05/2018
• Est. Priority Date: 09/29/2011
• Status: Active Grant

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic), Stealth BioTherapeutics, Inc. (Morningside Group Ltd.)
• Original Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic), Stealth BioTherapeutics Corp. (Morningside Group Ltd.)
• Inventors: Wilson, D. Travis, Lerman, Lilach O., Textor, Stephen C.
• Primary Examiner(s): Garyu, Lianko G
• Application Number:
  US14/347,998
• Publication Number:
  US 20140235529A1
• Time in Patent Office: 2,076 Days
• Field of Search: None
• 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 38/06 Tripeptides
• 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 13/12 of the kidneys
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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
• CPC Class Codes: C07K 5/0817 the first amino acid being Arg

Abstract

The present disclosure provides methods of preventing or treating renal ischemia-reperfusion injury in a mammalian subject and methods for chronic treatment of ARVD, including administering an effective amount of an aromatic-cationic peptide to a subject in need thereof. The methods include administering aromatic-cationic peptides to prevent or treat renal injury during the treatment of renal artery stenosis. The methods include administering an effective amount of an aromatic-cationic peptide to subjects in need thereof.

Claims

1. A method for therapeutic treatment of atherosclerotic renal artery stenosis in a 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, and further comprising the step of performing a revascularization procedure on the subject, wherein the revascularization procedure comprises administration of one or more thrombolytic agents, and wherein the subject is administered the peptide prior to onset of renal microvasculature rarefaction.

2. The method of claim 1, wherein the revascularization procedure comprises percutaneous transluminal renal angioplasty.

3. The method of claim 1, 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.

4. The method of claim 3, 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.

5. The method of claim 3, 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.

6. The method of claim 1, wherein the revascularization procedure comprises removal of a renal artery occlusion.

7. The method of claim 1, 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.