Inhibition of sgk1 in the treatment of heart conditions

Abstract

The present invention relates to the treatment of acquired and genetic heart conditions in a subject by the inhibition of SGK1, including Long QT syndrome and cardiovascular disease, including dilated cardiomyopathy. Cardiovascular diseases treatable by SGK1 inhibition include heart failure, arrhythmia, ischemic injury, ischemic infarction, cardiac fibrosis, vascular proliferation, restenosis, dilated cardiomyopathy, and stent failure. The present invention also identifies selective inhibitors of SGK1. The method comprises administering to the subject a therapeutically effective amount of an inhibitor of SG.

1 . A method for treating a subject for Long QT syndrome, comprising administering to the subject a therapeutically effective amount of at least one SGK1 inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the Long QT syndrome is genetic. 
     
     
         3 . The method of  claim 1 , wherein the Long QT syndrome is acquired. 
     
     
         4 . The method of  claim 2 , wherein the genetic long QT Syndrome is characterized by a mutation in the KCNQ1 gene. 
     
     
         5 . The method of  claim 2 , wherein the genetic Long QT Syndrome is characterized by a mutation in the KCNH2 gene. 
     
     
         6 . The method of  claim 2  wherein the genetic Long QT Syndrome is characterized by a mutation in the SCN5a gene. 
     
     
         7 . The method of  claim 4 , wherein the genetic Long QT is characterized by a loss of function in the KCNQ1 gene. 
     
     
         8 . The method of  claim 5 , wherein the genetic Long QT is characterized by a loss of function in the KCNH2 gene. 
     
     
         9 . The method of  claim 6 , wherein the genetic Long QT is characterized by a gain in function in the SCN5a gene. 
     
     
         10 . A method for treatment of a cardiovascular disease in a subject, the method comprising, administering to the subject a therapeutically effective amount of at least one SGK1 inhibitor, wherein the cardiovascular disease is selected from the group consisting of heart failure, arrhythmia, ischemic injury, ischemic infarction, cardiac fibrosis, vascular proliferation, restenosis, dilated cardiomyopathy, and stent failure. 
     
     
         11 - 21 . (canceled) 
     
     
         22 . The method of  claim 10 , wherein the dilated cardiomyopathy is characterized by a mutation in the MYH6 gene. 
     
     
         23 . The method of  claim 10 , wherein the dilated cardiomyopathy is characterized by a mutation in the MYH7 gene. 
     
     
         24 . The method of  claim 10 , wherein the dilated cardiomyopathy is characterized by a mutation in the SCN5A gene. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 1 , wherein the SGK1 inhibitor is an anti-SGK1 antibody, or antigen-binding fragment thereof. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 1 , wherein the SGK-1 inhibitor is a polypeptide decoy mimicking a domain necessary for the function of SGK1, a peptidomimetic, a peptide inhibiting the function of SGK1, a miRNA, a siRNA, shRNA, a dsRNA or an antisense RNA directed to SGK1 DNA or mRNA. 
     
     
         30 . The method of  claim 1 , wherein the SGK1 inhibitor is a polynucleotide encoding: a polypeptide decoy mimicking a domain necessary for the function of SGK1, a peptidomimetic, a peptide interfering with the function of SGK1, a miRNA, a siRNA, shRNA, a dsRNA, a dominant negative mutant of SGK1 or an antisense RNA directed to SGK1 DNA or mRNA. 
     
     
         31 . The method of  claim 10 , wherein the SGK1 inhibitor is an anti-SGK1 antibody, or antigen-binding fragment thereof. 
     
     
         32 . The method of  claim 10 , wherein the SGK-1 inhibitor is a polypeptide decoy mimicking a domain necessary for the function of SGK1, a peptidomimetic, a peptide inhibiting the function of SGK1, a miRNA, a siRNA, shRNA, a dsRNA or an antisense RNA directed to SGK1 DNA or mRNA. 
     
     
         33 . The method of  claim 10 , wherein the SGK1 inhibitor is a polynucleotide encoding: a polypeptide decoy mimicking a domain necessary for the function of SGK1, a peptidomimetic, a peptide interfering with the function of SGK1, a miRNA, a siRNA, shRNA, a dsRNA, a dominant negative mutant of SGK1 or an antisense RNA directed to SGK1 DNA or mRNA.