Use of hdac and/or dnmt inhibitors for treatment of ischemic injury

Abstract

The present invention provides methods of ameliorating or reducing the extent of ischemic injury, reperfusion injury, and myocardial infarction, by administering an inhibitor of histone deacetylase enzyme (HDAC) or an inhibitor of DNA methyltransferase enzyme (DNMT).

What is claimed is: 
     
         1 . Use of an inhibitor of a histone deacetylase (HDAC) for the preparation of a pharmaceutical composition for ameliorating an ischemic injury. 
     
     
         2 . Use of an inhibitor of a histone deacetylase (HDAC) for the preparation of a pharmaceutical composition for reducing an extent of an ischemic injury. 
     
     
         3 . Use of an inhibitor of a histone deacetylase (HDAC) for the preparation of a pharmaceutical composition for reducing a size of a myocardial infarction. 
     
     
         4 . Use of an inhibitor of a histone deacetylase (HDAC) for the preparation of a pharmaceutical composition for reducing a morbidity of a myocardial infarction. 
     
     
         5 . The use of any of  claims 1 - 4 , wherein said inhibitor of an HDAC is a trichostatin A. 
     
     
         6 . The use of any of  claims 1 - 4 , wherein said inhibitor of an HDAC is Scriptaid, a valproic acid, FK228, or PXD101. 
     
     
         7 . The use of any of  claims 1 - 6 , wherein said pharmaceutical composition further further comprises an inhibitor of a DNA methyltransferase (DNMT). 
     
     
         8 . Use of an inhibitor of a DNA methyltransferase (DNMT) for the preparation of a pharmaceutical composition for ameliorating an ischemic injury. 
     
     
         9 . Use of an inhibitor of a DNA methyltransferase (DNMT) for the preparation of a pharmaceutical composition for reducing an extent of an ischemic injury. 
     
     
         10 . Use of an inhibitor of a DNA methyltransferase (DNMT) for the preparation of a pharmaceutical composition for reducing a size of a myocardial infarction. 
     
     
         11 . Use of an inhibitor of a DNA methyltransferase (DNMT) for the preparation of a pharmaceutical composition for reducing a morbidity of a myocardial infarction. 
     
     
         12 . The use of any of  claims 8 - 11 , wherein said inhibitor of a DNMT is a 5-aza-cytidine or a 5-aza-2′-deoxycytidine. 
     
     
         13 . The use of any of  claims 1 ,  2 ,  5 - 7 ,  8 ,  9 , and  12 , wherein said ischemic injury is in a cardiac tissue. 
     
     
         14 . The use of any of  claims 1 ,  2 ,  5 - 7 ,  8 ,  9 , and  12 , wherein said ischemic injury is in a cardiac muscle tissue. 
     
     
         15 . The method of any of  claims 1 ,  2 ,  5 - 7 ,  8 ,  9 , and  12 , wherein said ischemic injury is from a cardiac surgery. 
     
     
         16 . The use of  claim 15 , wherein said inhibitor of an HDAC or inhibitor of a DNMT is administered to said subject before or during said cardiac surgery. 
     
     
         17 . The use of  claim 15 , wherein said inhibitor of an HDAC or inhibitor of a DNMT is administered to said subject within one hour after said cardiac surgery. 
     
     
         18 . The method of any of  claims 1 ,  2 ,  5 - 7 ,  8 ,  9 , and  12 , wherein said ischemic injury is in a brain tissue or a lung tissue. 
     
     
         19 . The method of any of  claims 1 ,  2 ,  5 - 7 ,  8 ,  9 , and  12 , wherein said ischemic injury is from a stroke. 
     
     
         20 . The method of  claim 19 , wherein said inhibitor of an HDAC or inhibitor of a DNMT is administered to said subject within one hour after said stroke. 
     
     
         21 . The method of any of  claims 3 ,  4 ,  10 , and  11 , wherein said inhibitor of an HDAC or inhibitor of a DNMT is administered to said subject within one hour after said myocardial infarction. 
     
     
         22 . A method of identifying a compound useful for a treatment or inhibition of an ischemic injury to a tissue, comprising
 a. contacting a first sample of said tissue or an extract thereof with said compound;   b. determining an experimental histone deacetylase (HDAC) activity level of said first sample or extract thereof;   c. determining a control HDAC activity level of a second sample of said tissue or an extract thereof, wherein said second sample of or extract thereof has not been contacted with said compound; and   d. comparing said experimental HDAC activity level with said control HDAC activity level;   
       wherein a reduction of said HDAC activity by said test compound indicates utility of said test compound for a treatment or inhibition of an ischemic injury to said tissue. 
     
     
         23 . A method of identifying a compound useful for a treatment or inhibition of an ischemic injury to a tissue, comprising
 a. contacting a first sample of said tissue or an extract thereof with said compound;   b. determining an experimental DNA methyltransferase (DNMT) activity level of said first sample or extract thereof;   c. determining a control DNMT activity level of a second sample of said tissue or an extract thereof, wherein said second sample of or extract thereof has not been contacted with said compound; and   d. comparing said experimental DNMT activity level with said control DNMT activity level;   
       wherein a reduction of said DNMT activity by said test compound indicates utility of said test compound for a treatment or inhibition of an ischemic injury to said tissue.