Methods and compositions for modulating mitochondrial alderhyde dehydrogenase-2

Abstract

The present invention provides screening methods for identifying agents that modulate the activity of mitochondrial aldehyde dehydrogenase-2 (AldDH2), as well as agents identified by the screening methods. The present invention further provides methods of reducing ischemic tissue damage or free-radical induced damage in an organ, the methods generally involving contacting the organ with an agent that increases AldDH2 levels and/or activity. The present invention further provides methods of treating solid tumors, the methods generally involving administering an agent that decreases AldDH2 levels and/or activity.

1 .- 17 . (canceled) 
     
     
         18 . A method of treating an ischemic condition in an individual in need thereof, the method comprising administering to the individual an effective amount of an agent that increases the level and/or activity of mitochondrial aldehyde dehydrogenase in a cell of a tissue that is ischemic. 
     
     
         19 . The method of  claim 18 , wherein the ischemic condition is cardiac ischemia. 
     
     
         20 . A method of treating a chronic free-radical associated disease in an individual in need thereof, the method comprising administering to the individual an effective amount of an agent that increases the level and/or activity of mitochondrial aldehyde dehydrogenase in a cell of the individual. 
     
     
         21 . A method of treating a solid tumor in an individual, the method comprising administering to the individual an effective amount of an agent that decreases the level and/or activity of mitochondrial aldehyde dehydrogenase in a tumor cell in the individual. 
     
     
         22 . The method of  claim 21 , wherein the agent is administered as an adjuvant to a standard therapy for cancer. 
     
     
         23 . The method of  claim 22 , wherein the standard cancer therapy is radiation therapy. 
     
     
         24 . The method of  claim 22 , wherein the standard cancer therapy is chemotherapy. 
     
     
         25 . The method of  claim 21 , wherein said administration is intratumoral or peritumoral. 
     
     
         26 . The method of  claim 18 , wherein said individual is a human. 
     
     
         27 . The method of  claim 18 , wherein said agent is administered by a route selected from intravenous, oral, intramuscular, and intratracheal. 
     
     
         28 . The method of  claim 18 , wherein said agent is administered before an ischemic event. 
     
     
         29 . The method of  claim 20 , wherein said individual is a human. 
     
     
         30 . The method of  claim 20 , wherein said chronic free radical associated disease is a neurodegenerative disease. 
     
     
         31 . The method of  claim 21 , wherein said individual is a human.