Compositions and Methods for Modulating Cardiac Conditions

Abstract

Embodiments herein report methods and compositions for treating cardiac conditions. In certain embodiments, compositions and methods relate to reducing, inhibiting or treating a subject having or suspected of undergoing cardiac remodeling after a cardiac event. Other embodiments herein relate to compounds including naturally occurring and synthetic compositions of alpha-1 antitrypsin and fragments thereof.

What is claimed is: 
     
         1 - 22 . (canceled) 
     
     
         23 . A method for treating a subject suffering from a cardiac event,
 selecting the subject having a cardiac event comprising acute myocardial infarction (AMI); and   administering a therapeutically effective amount of a composition comprising one or more of alpha-1 antitrypsin (AAT), a fragment thereof, a fusion molecule thereof or a mutant thereof, wherein administering the composition comprises administering at the time of reperfusion of the subject.   
     
     
         24 . The method of  claim 23 , wherein the composition comprises naturally occurring AAT (SEQ ID NO:1). 
     
     
         25 . The method of  claim 23 , wherein the composition comprises a composition of one or more carboxyterminal fragments of naturally occurring AAT. 
     
     
         26 . The method of  claim 23 , administering at least a second dose of the composition to the subject within days after the cardiac event. 
     
     
         27 . The method of  claim 23 , wherein the composition reduces left ventricle end-diastolic diameters (LVEDD) and left ventricle end-systolic diameters (LVESD) in the subject compared to a control subject not receiving the composition. 
     
     
         28 . The method of  claim 23 , wherein the composition is administered to the subject daily for several days after the event. 
     
     
         29 . The method of  claim 23 , wherein caspase-1 is measured before, during or after administration of the composition to the subject. 
     
     
         30 . The method of  claim 23 , wherein the composition comprising alpha-1 antitrypsin (AAT) is a fusion molecule having AAT fused to a human IgG or fragment of human IgG. 
     
     
         31 . The method of  claim 23 , further comprising the step of assessing LVEDD and LVESD in the subject within 24 hours of administering the composition to the subject. 
     
     
         32 . The method of  claim 23 , further comprising assessing LVEDD and LVESD at least one additional time following administering the composition to the subject. 
     
     
         33 . The method of  claim 23 , wherein the composition reduces infarct size in the subject. 
     
     
         34 . The method of  claim 33 , wherein the composition reduces infarct size by at least 10% compared to a subject not having the composition. 
     
     
         35 . The method of  claim 23 , wherein the therapeutically effective amount of the composition comprises a single intravenous infusion in the subject of AAT at a dose from 20 mg/kg to 70 mg/kg, optionally followed by additional treatments with the composition. 
     
     
         36 . The method of  claim 23 , further comprising analyzing blood samples from the subject for levels of active agent(s) after administration. 
     
     
         37 . A method for reducing monocyte chemoattractant protein-1 (MCP-1) production in a subject comprising, treating the subject with a composition comprising alpha-1 antitrypsin (AAT), a fusion molecule thereof, a fragment thereof or a mutant thereof wherein the composition reduces the level of MCP-1 in the subject compared to a control subject not receiving the composition. 
     
     
         38 . The method of  claim 37 , wherein the composition reduces MCP-1 by at least 10% compared to a subject not having the composition.