Compositions and methods for treating and preventing cardiomyopathy and heart disease
The present invention relates to compositions and methods for treating and preventing heart disease. In particular, the present invention provides compositions comprising poloxamers (e.g., poloxamer 188-P188) and methods of using the same for treating and preventing heart disease (e.g., in subjects with muscular dystrophy) and for treating cells and tissue damage caused by ischemia and cell death (e.g., for treating dystrophin-deficient cells (e.g., myocytes)).
1. A method of treating a subject with diastolic dysfunction comprising administering to said subject a composition consisting of poloxamer-188 and a buffer under conditions such that said diastolic dysfunction is improved in said subject.
2. The method of claim 1 , wherein said poloxamer-188 is a purified or fractionated poloxamer.
3. The method of claim 1 , wherein said subject is a human subject.
4. The method of claim 1 , wherein said composition is administered via intravenous administration.
5. The method of claim 1 , wherein improvement in said diastolic dysfunction comprises an improvement in left ventricular function in said subject.
6. The method of claim 1 , wherein said subject is a dystrophin deficient subject.
7. The method of claim 6 , wherein said subject has Duchene muscular dystrophy.
8. The method of claim 3 , wherein said treating decreases susceptibility to calcium overload in heart tissue of said subject.
9. The method of claim 8 , wherein decreasing susceptibility to calcium overload in heart tissue of said subject comprises lowering intracellular Ca 2+ levels in cardiac myocytes of said subject.
10. The method of claim 9 , wherein said lowering intracellular Ca 2+ levels in cardiac myocytes prevents remodeling or reverses remodeling of cardiac muscle tissue in said subject.
11. The method of claim 1 , wherein said treating decreases cell contracture and cell death in the heart tissue of said subject.
12. The method of claim 1 , wherein said composition consisting of poloxamer-188 is co-administered with one or more agents selected from the group consisting of a diuretic, a loop diuretic, a potassium sparing agent, a vasodilator, an ACE inhibitor, an angiotensin II antagonist, a positive inotropic agent, a phosphodiesterase inhibitor, a beta-adrenergic receptor antagonist, a calcium channel blocker, a nitrate, an alpha blocker, a central alpha antagonist, a statin, or a combination of these agents.