Neuregulin based methods and compositions for treating cardiovascular diseases

Abstract

The present invention relates to compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders in mammals, particularly in humans. More particularly, the present invention provides for compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders using, inter alia, a neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a neuregulin protein, or a functional fragment thereof, or an agent that enhances production and/or function of said neuregulin.

1 . A combination, which combination comprises an effective amount of a neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a neuregulin protein, or a functional fragment thereof, or an agent that enhances production and/or function of said neuregulin, and an effective amount of a prophylactic or therapeutic agent for viral myocarditis or dilated (congestive) cardiomyopathy (DCM). 
     
     
         2 - 5 . (canceled) 
     
     
         6 . The combination of  claim 1 , wherein the prophylactic or therapeutic agent for viral myocarditis is selected from the group consisting of an antibiotic, a heart protective agent, an antioxidant and a nutrient for myocardium. 
     
     
         7 - 10 . (canceled) 
     
     
         11 . The combination of  claim 1 , wherein the prophylactic or therapeutic agent for DCM is selected from the group consisting of a cardiac tonic, a diuretic, an angiotensin I-converting enzyme inhibitor (ACEI), a calcium antagonist and a β-receptor antagonist. 
     
     
         12 - 16 . (canceled) 
     
     
         17 . A kit, which kit comprises a combination of  claim 1  in a container and an instruction for using said combination in preventing, treating or delaying viral myocarditis or DCM. 
     
     
         18 . A method for preventing, treating or delaying viral myocarditis or dilated (congestive) cardiomyopathy (DCM) in a mammal, which method comprises administering to a mammal, to which such prevention, treatment or delay is needed or desirable, an effective amount of the combination of  claim 1 , whereby said viral myocarditis or DCM is prevented, treated or delayed. 
     
     
         19 - 46 . (canceled) 
     
     
         47 . A pharmaceutical composition for preventing, treating or delaying viral myocarditis or dilated (congestive) cardiomyopathy (DCM) in a mammal, which pharmaceutical composition comprises an effective amount of a neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a NRG protein, or a functional fragment thereof, or an agent that enhances production and/or function of said neuregulin. 
     
     
         48 - 51 . (canceled) 
     
     
         52 . The pharmaceutical composition of  claim 47 , wherein the neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a neuregulin protein, or a functional fragment thereof, has a dosage range from about 25 μg to about 2,500 μg. 
     
     
         53 . A kit, which kit comprises a pharmaceutical composition of  claim 47 , in a container and an instruction for using said pharmaceutical composition in preventing, treating or delaying viral myocarditis or DCM. 
     
     
         54 . A method for preventing, treating or delaying cardiac toxicity in a mammal to which such prevention, treatment or delay is needed or desirable, comprising administering to a mammal in vivo an effective amount of a prophylactic or a therapeutic agent and an effective amount of the pharmaceutical composition of  claim 47 , whereby said cardiac toxicity associated with administration of said prophylactic or therapeutic agent is prevented, treated or delayed. 
     
     
         55 - 82 . (canceled) 
     
     
         83 . A combination, which combination comprises an effective amount of a neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a neuregulin protein, or a functional fragment thereof, or an agent that enhances production and/or function of said neuregulin, and an effective amount of a prophylactic or therapeutic agent for myocardial infarction. 
     
     
         84 - 87 . (canceled) 
     
     
         88 . The combination of  claim 83 , wherein the prophylactic or therapeutic agent for viral myocarditis is selected from the group consisting of an angiotensin I-converting enzyme inhibitor (ACEI), a calcium antagonist, a P-receptor antagonist, aspirin, atropine, nitroglycerin, scopolamine and a thrombolytic agent. 
     
     
         89 . The combination of  claim 88 , wherein the ACEI is selected from the group consisting of Captopril, Rampril, Lisinopril, Zofenopril and Trandolapril. 
     
     
         90 . The combination of  claim 88 , wherein the calcium antagonist is diltiazem. 
     
     
         91 . The combination of  claim 88 , wherein the P-receptor antagonist is selected from the group consisting of propranolol, metoprolol, atenolol and timolol. 
     
     
         92 . The combination of  claim 88 , wherein the thrombolytic agent is selected from the group consisting of streptokinase, t-PA and anistreplase. 
     
     
         93 . The combination of  claim 83 , which further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         94 . A kit, which kit comprises a combination of  claim 83  in a container and an instruction for using said combination in preventing, treating or delaying myocardial infarction. 
     
     
         95 . A method for preventing, treating or delaying myocardial infarction in a mammal, which method comprises administering to a mammal, to which such prevention, treatment or delay is needed or desirable, an effective amount of the combination of  claim 83 , whereby said myocardial infarction is prevented, treated or delayed. 
     
     
         96 - 124 . (canceled)