Methods and compositions for the prevention or treatment of barth syndrome

• US 9,687,519 B2
• Filed: 02/28/2014
• Issued: 06/27/2017
• Est. Priority Date: 03/01/2013
• Status: Active Grant

• Current Assignee: Stealth BioTherapeutics, Inc. (Morningside Group Ltd.)
• Original Assignee: Stealth BioTherapeutics Corp. (Morningside Group Ltd.)
• Inventors: Wilson, D. Travis, Bamberger, Mark
• Primary Examiner(s): Russel, Jeffrey E
• Application Number:
  US14/771,408
• Publication Number:
  US 20160228487A1
• Time in Patent Office: 1,215 Days
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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

Abstract

The disclosure provides methods of preventing or treating Barth Syndrome in a mammalian subject, reducing risk factors associated with Barth Syndrome, and/or reducing the likelihood or severity of Barth Syndrome. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to increase expression of TAZ1 in subjects in need thereof.

Claims

1. A method for stabilizing cardiolipin remodeling in a mammalian subject having or suspected of having Barth Syndrome comprising administering to the subject a therapeutically effective amount of the peptide D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂ or a pharmaceutically acceptable salt thereof, wherein the mammalian subject has decreased expression of TAZ1 compared to a normal control subject.

2. The method of claim 1, wherein the cardiolipin is 18:

2 species of cardiolipin.

3. The method of claim 1, wherein the subject is 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 1, wherein the pharmaceutically acceptable salt comprises acetate or trifluoroacetate salt.