Methods and compositions for the prevention or treatment of Barth Syndrome
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.
1. A method for treating cardiomyopathy 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-NH 2 or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the cardiomyopathy is associated with heart failure.
3. The method of claim 1 , wherein the cardiomyopathy is associated with LV dysfunction.
4. The method of claim 1 , wherein the cardiomyopathy is associated with dilated cardiomyopathy.
5. The method of claim 1 , wherein the cardiomyopathy is associated with ventricular arrhythmia.
6. The method of claim 1 , wherein the cardiomyopathy is associated with cardiac hypertrophy.
7. The method of claim 1 , wherein the subject is human.
8. The method of claim 1 , wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.
9. The method of claim 1 , wherein the mammalian subject has decreased expression of TAZ1 compared to a normal control subject.
10. The method of claim 1 , wherein administration of the peptide lessens the severity of the cardiomyopathy.
11. The method of claim 1 , wherein administration of the peptide delays the onset of the cardiomyopathy.
12. The method of claim 1 , wherein administration of the peptide delays progression of the cardiomyopathy.
13. The method of claim 3 , wherein administration of the peptide improves LV function and the rate of mitochondrial ATP synthesis.
14. The method of claim 1 further comprising separately, sequentially or simultaneously administering a cardiovascular agent to the subject.
15. The method of claim 14 , wherein the cardiovascular agent is selected from the group consisting of: an anti-arrhythmia 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 thromboxane 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, and an antihyperlipidemic drug.