Compositions and methods for treating heart disease and/or injury

Abstract

A method of treating heart disease and/or injury in a subject includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ.

Having described the invention, we claim: 
     
         1 . A method of treating heart disease or injury in a subject in need thereof, the method comprising:
 administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ.   
     
     
         2 . The method of  claim 1 , the therapeutic agent comprising a therapeutic peptide, the therapeutic peptide having an amino acid sequence that is at least about 85% homologous to about 10 to about 20 consecutive amino acids of the wedge domain of PTPσ. 
     
     
         3 . The method of  claim 1 , the therapeutic agent comprising a therapeutic peptide, the therapeutic peptide having an amino acid sequence that is at least about 95% homologous to about 10 to about 20 consecutive amino acids of the wedge domain of PTPσ. 
     
     
         4 . The method of  claim 1 , the therapeutic agent comprising a therapeutic peptide selected from the group consisting of SEQ ID NOs: 1-25 and 32. 
     
     
         5 . The method of  claim 1 , the therapeutic agent comprising a therapeutic peptide consisting of SEQ ID NO: 32. 
     
     
         6 . The method of  claim 5 , the therapeutic peptide including a conservative substitution of an amino acid of at least one of residue 4, 5, 6, 7, 9, 10, 12, or 13 of SEQ ID NO: 32. 
     
     
         7 . The method of any of  claims 4 , wherein the therapeutic agent includes a transport moiety that is linked to the therapeutic peptide and facilitates uptake of the therapeutic peptides by a cell of the heart being treated. 
     
     
         8 . The method of  claim 7 , wherein the transport moiety is an HIV Tat transport moiety. 
     
     
         9 . The method of  claim 7 , wherein the therapeutic agent is administered systemically to the subject being treated. 
     
     
         10 . The method of any of  claim 4 , wherein the therapeutic agent is expressed in a cell of the heart. 
     
     
         11 . The method of  claim 1 , wherein the heart disease or injury comprises at least one of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac denervation hypersensitivity, or arrhythmia. 
     
     
         12 . The method of  claim 11 , wherein the heart injury is a myocardial infarction and the therapeutic agent is administered to the infarct or peri-infarct region of the heart. 
     
     
         13 . A method of treating arrhythmia in a subject in need thereof, the method comprising:
 administering to cardiac tissue of the subject a therapeutically effective amount of a therapeutic agent that inhibits one or more of catalytic activity, signaling, and/or function of PTPσ.   
     
     
         14 . The method of  claim 13 , the therapeutic agent comprising a therapeutic peptide, the therapeutic peptide having an amino acid sequence that is at least about 85% homologous to about 10 to about 20 consecutive amino acids of the wedge domain of PTPσ. 
     
     
         15 . The method of  claim 13 , the therapeutic agent comprising a therapeutic peptide, the therapeutic peptide having an amino acid sequence that is at least about 95% homologous to about 10 to about 20 consecutive amino acids of the wedge domain of PTPσ. 
     
     
         16 . The method of  claim 13 , the therapeutic agent comprising a therapeutic peptide selected from the group consisting of SEQ ID NOs: 1-25 and 32. 
     
     
         17 . The method of  claim 13 , the therapeutic agent comprising a therapeutic peptide consisting of SEQ ID NO: 32. 
     
     
         18 . The method of  claim 13 , the therapeutic agent comprising a therapeutic peptide that is at least about 65% homologous to SEQ ID NO: 32. 
     
     
         19 . The method of  claim 18 , the therapeutic peptide including a conservative substitution of an amino acid of at least one of residue 4, 5, 6, 7, 9, 10, 12, or 13 of SEQ ID NO: 32. 
     
     
         20 . The method of any of  claims 19 , wherein the therapeutic agent includes a transport moiety that is linked to the therapeutic peptide and facilitates uptake of the therapeutic peptides by a cell of the heart being treated. 
     
     
         21 . The method of  claim 20 , wherein the transport moiety is an HIV Tat transport moiety. 
     
     
         22 . The method of  claim 20 , wherein the therapeutic agent is administered systemically to the subject being treated. 
     
     
         23 . The method of any of  claim 19 , wherein the therapeutic agent is expressed in a cardiac nerve cell.