Therapies for cardiomyopathy

Abstract

The present invention relates to therapies and therapeutic agents for use in the treatment of cardiomyopathies. In particular, the invention is concerned with, but not limited to therapies and therapeutic agents for use in the treatment of hypertrophic cardiomyopathy. Such therapeutic agents comprise hypomethylating agents.

1 . A hypomethylating agent for use in the prevention or treatment of cardiomyopathy. 
     
     
         2 . The hypomethylating agent of  claim 1  wherein the agent comprises 5-Azacytidine or 5-Aza-2′-Deoxycytidine. 
     
     
         3 . The hypomethylating agent of  claim 1  for use in the prevention or treatment of ischemic or non-ischemic cardiomyopathy. 
     
     
         4 . The hypomethylating agent of  claim 1  for use in the prevention or treatment of a cardiomyopathy selected from the group consisting of hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and endomyocardial fibrosis. 
     
     
         5 . The hypomethylating agent of  claim 1  for use in the prevention or treatment of hypertrophic cardiomyopathy. 
     
     
         6 . The hypomethylating agent of  claim 1  for use in the prevention or treatment of cardiomyopathy, which is independent of hypertension. 
     
     
         7 . The hypomethylating agent of  claim 5  wherein the agent has the effect of inhibiting the expression or action of DNA methyltransferase1, DNA methyltransferase3A, or DNA methyltransferase3B. 
     
     
         8 . A method of identifying a therapeutic agent capable of preventing or treating cardiomyopathy comprising testing the ability of possible therapeutic agents to modify expression and/or action of one or more of the following genes involved in hypertrophic cardiomyopathy: MYH7, MYBPC3, TNNT2, TNNI3, TPM 1, MYL2, MYL3, ACTC1, CSRP3, TTN, ACTN2, MYH6, TCAP, TNNC1, ACTA1. 
     
     
         9 . The method of  claim 8  comprising testing the ability of possible therapeutic agents to increase the expression and/or action of one or both of the genes cardiac myosin binding protein-C(MYBPC3) and ACTA1. 
     
     
         10 . An agent capable of reducing the expression of, silencing or degrading HIF protein or HIF mRNA for use in the prevention or treatment of cardimyopathy or myocardial fibrosis. 
     
     
         11 . The agent of  claim 10  comprising a monoclonal antibody, a peptide or a small molecule capable of interacting with HIF protein and preventing its binding to hypoxia responsive elements within the promoter regions of DNA methyltransferase genes. 
     
     
         12 . The agent of  claim 10  comprising a monoclonal antibody, a peptide, an oligonucleotide or a small molecule capable of binding to hypoxia responsive elements within the promoter regions of DNA methyltransferase genes, thereby preventing binding of HIF to said elements. 
     
     
         13 . The agent of  claim 10  comprising the siRNA of SEQID 31. 
     
     
         14 . A method of identifying a therapeutic agent capable of preventing or treating cardiomyopathy or fibrosis comprising:
 testing the ability of putative therapeutic agents to reduce the expression of, degrade or silence HIF protein or HIF mRNA; and/or   testing the ability of putative therapeutic agents to prevent HIF protein from binding to hypoxia responsive elements within the promoter regions of DNA methyltransferase genes.   
     
     
         15 . A method of preventing or treating cardiomyopathy or myocardial fibrosis comprising the use of a hypomethylating agent. 
     
     
         16 . A method of preventing or treating cardiac hypertrophy or myocardial fibrosis comprising administering to a subject in need thereof an agent capable of reducing the expression of, silencing or degrading HIF protein or HIF mRNA, or an agent capable of preventing HIF protein from binding to hypoxia responsive elements within the promoter regions of DNA methyltransferase genes.