Method and composition for treating heart failure

Abstract

A method and composition for treating, preventing or ameliorating heart failure, cardiac hypertrophy, and/or myocardial dysfunction includes administering a therapeutically effective amount of a HDAC inhibitor, such as phenylbutyrate, in combination with an ACE inhibitor, such as captopril.

1 . A method of treating or preventing heart failure, comprising:
 administering to a subject in need thereof a therapeutically effective amount of a composition including a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or ester thereof, and an angiotensin converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta adrenergic receptor blocker, or a pharmaceutically acceptable salt or ester thereof.   
     
     
         2 . The method of treating or preventing heart failure of  claim 1 , wherein:
 the HDAC inhibitor comprises phenylbutyrate.   
     
     
         3 . The method of treating or preventing heart failure of  claim 2 , wherein:
 the ACE inhibitor comprises captopril.   
     
     
         4 . The method of treating or preventing heart failure of  claim 1 , wherein:
 the composition is administered orally or non-orally.   
     
     
         5 . The method of treating or preventing heart failure of  claim 1 , wherein:
 an oral dose of the HDAC inhibitor or a pharmaceutically acceptable salt or ester thereof comprises about 1 to 30 grams per day with the ACE inhibitor about 0.001 to 1.0 gram per day.   
     
     
         6 . The method of treating or preventing heart failure of  claim 1 , wherein:
 the composition comprises an injection solution, drip infusion formulation, or a patch.   
     
     
         7 . The method of treating or preventing heart failure of  claim 1 , wherein:
 the subject may exhibit one or more symptoms of heart failure, cardiac hypertrophy, and myocardial dysfunction.   
     
     
         8 . A method of reversing or preventing cardiac gene expression changes associated with heart failure, comprising:
 administering to a subject in need thereof a therapeutically effective amount of a composition including a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or ester thereof, and an angiotensin converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta adrenergic receptor blocker, or a pharmaceutically acceptable salt or ester thereof.   
     
     
         9 . A method of reducing or preventing left ventricular hypertrophy, comprising:
 administering to a subject in need thereof a therapeutically effective amount of a composition including a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or ester thereof, and an angiotensin converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta adrenergic receptor blocker, or a pharmaceutically acceptable salt or ester thereof.   
     
     
         10 . A method of reversing or preventing myocardial dysfunction, comprising:
 administering to a subject in need thereof a therapeutically effective amount of a composition including a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or ester thereof, and an angiotensin converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta adrenergic receptor blocker, or a pharmaceutically acceptable salt or ester thereof.