Compositions and Methods for Modulating Cardiac Conditions
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.
1 - 22 . (canceled)
23 . A method for treating a subject suffering from a cardiac event,
identifying a subject having 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, to the subject 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 compared to a control subject not having 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.