Compositions and methods for cardiac tissue protection and regeneration

Abstract

In various aspects the present inventions provide compositions and methods for treatment of cardiac conditions. In various embodiments, the present inventions provide methods for treating a cardiac condition comprising the step of administering in a therapeutically effective amount the substantially cell free solution of an amphiphilic self-assembling peptide to a site of cardiac tissue that has been injured due to one or more of atrial fibrillation, acute myocardial infarction; valve disease, pericardial disease, congenital heart disease, congestive heart failure, and embolism.

1 . A method for treating a cardiac condition comprising the steps of:
 providing a substantially cell free solution comprising at least about 1% by weight of amphiphilic self-assembling peptides with an amino acid sequence comprising RADARADARADARADA (SEQ. ID NO. 1); and   administering in a therapeutically effective amount the substantially cell free solution to a site of cardiac tissue that has been injured due to one or more of atrial fibrillation, acute myocardial infarction; valve disease, pericardial disease, congenital heart disease, and congestive heart failure.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the amphiphilic self-assembling peptide comprises a RADARADARADARADA (SEQ. ID NO. 1) sequence modified with one or more additional sequences. 
     
     
         4 . The method of  claim 1 , wherein the step of administering comprises administering the self-assembling peptide in an amount sufficient to reduce one or more of infarct size, infarct expansion, ventricular wall stress, and atrial fibrillation. 
     
     
         5 . The method of  claim 1 , wherein the step of administering comprises locally delivering nitric oxide to the site of cardiac tissue injury. 
     
     
         6 . The method of  claim 5 , wherein the nitric oxide is locally delivered by one or more of formation from the L-arginine (LA) peptide sequence present in the self-assembling peptide and formation in response to a stimuli provided by the self-assembling peptide. 
     
     
         7 . The method of  claim 1 , wherein the step of administering comprises injecting the amphiphilic self-assembling peptide into the cardiac tissue. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the substantially cell free solution contains greater than about 3% by weight of an amphiphilic self-assembling peptide comprised of a RADARADARADARADA (SEQ. ID NO. 1) sequence. 
     
     
         10 . The method of  claim 1 , wherein the substantially cell free solution comprises a physiologically acceptable concentration of sucrose. 
     
     
         11 . The method of  claim 1 , wherein the substantially cell free solution comprises one or more of a growth factor and therapeutic agent. 
     
     
         12 . A method for treating tissue injured by one or more of hypertension, septic shock, neuro-degeneration, arthritis, and asthma comprising the steps of:
 providing a substantially cell free solution comprising at least about 1% by weight of amphiphilic self-assembling peptides with an amino acid sequence comprising RADARADARADARADA (SEQ. ID NO. 1); and   administering in a therapeutically effective amount the substantially cell free solution to the tissue to be treated.   
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 12 , wherein the amphiphilic self-assembling peptide comprises a RADARADARADARADA (SEQ. ID NO. 1) sequence modified with one or more additional sequences. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 12 , wherein the substantially cell free solution contains greater than about 3% by weight of an amphiphilic self-assembling peptide comprised of a RADARADARADARADA (SEQ. ID NO.1) sequence. 
     
     
         17 . The method of  claim 12 , wherein the substantially cell free solution comprises a physiologically acceptable concentration of sucrose. 
     
     
         18 . The method of  claim 12 , wherein the substantially cell free solution comprises one or more of a growth factor and therapeutic agent. 
     
     
         19 . The method of  claim 12 , wherein the step of administering comprises injecting the substantially cell free solution into the tissue to be treated. 
     
     
         20 . The method of  claim 12 , wherein the step of administering comprises locally delivering nitric oxide to the tissue to be treated. 
     
     
         21 . The method of  claim 16 , wherein the nitric oxide is locally delivered by one or more of formation from the L-arginine (LA) peptide sequence present in the self-assembling peptide and formation in response to a stimuli provided by the self-assembling peptide. 
     
     
         22 . A method for providing a cardio-protective effect comprising the steps of:
 providing a substantially cell free solution comprising greater than about 1% by weight of amphiphilic self-assembling peptides with an amino acid sequence comprising RADARADARADARADA (SEQ. ID NO. 1); and   locally administering in a therapeutic effective amount the substantially cell free solution to cardiac tissue.   
     
     
         23 . The method of  claim 22 , wherein the substantially cell free solution provided comprises greater than about 3% by weight of amphiphilic self-assembling peptides with an amino acid sequence comprising RADARADARADARADA (SEQ. ID NO. 1). 
     
     
         24 . The method of  claim 22 , wherein the amphiphilic self-assembling peptides with an amino acid sequence comprising RADARADARADARADA (SEQ. ID NO. 1) is modified with one or more additional sequences. 
     
     
         25 . The method of  claim 22 , wherein the substantially cell free solution comprises a physiologically acceptable concentration of sucrose. 
     
     
         26 . The method of  claim 22 , wherein the substantially cell free solution comprises one or more of a growth factor and therapeutic agent. 
     
     
         27 . The method of  claim 22 , wherein the substantially cell free solution is locally administered in an amount sufficient to reduce reperfusion injury. 
     
     
         28 . A method for creating an embolism in a blood vessel comprising the steps of:
 providing a substantially cell free solution comprising at least about 1% by weight of amphiphilic self-assembling peptides with an amino acid sequence comprising RADARADARADARADA (SEQ. ID NO. 1); and   administering the substantially cell free solution into a blood vessel to create an embolization to at least partially reduce blood flow in the blood vessel.   
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 28 , wherein the amphiphilic self-assembling peptide comprises a RADARADARADARADA (SEQ. ID NO.1) sequence modified with one or more additional sequences. 
     
     
         31 . The method of  claim 28 , wherein the step of administering comprises injecting the substantially cell free solution around a tumor in or near the blood vessel. 
     
     
         32 . The method of claim,  28  wherein the step of administering comprises injecting the amphiphilic self-assembling peptide into a tumor. 
     
     
         33 . The method of claim,  28  wherein the step of administering comprises administering the amphiphilic self-assembling peptide by one or more of application onto and injection into a bleeding blood vessel in an amount sufficient to substantially stop the bleeding from the blood vessel. 
     
     
         34 . (canceled) 
     
     
         35 . The method of  claim 28 , wherein the substantially cell free solution contains greater than about 3% by weight of an amphiphilic self-assembling peptide comprised of a RADARADARADARADA (SEQ. ID NO. 1) sequence. 
     
     
         36 . The method of  claim 28 , wherein the substantially cell free solution comprises a physiologically acceptable concentration of sucrose. 
     
     
         37 . The method of  claim 28 , wherein the substantially cell free solution comprises one or more of a growth factor and therapeutic agent. 
     
     
         38 . A method for treating an infarct comprising the steps of:
 providing a substantially cell free solution comprising at least about 1% by weight of an amphiphilic self-assembling peptide with an amino acid sequence comprising RADARADARADARADA (SEQ. ID NO. 1); and   injecting the substantially cell free solution into the infarct.   
     
     
         39 . The method of  claim 38 , wherein the substantially cell free solution provided comprises greater than about 1% by weight of the RADARADARADARADA (SEQ. ID NO. 1) sequence. 
     
     
         40 . The method of  claim 38 , wherein the substantially cell free solution provided comprises greater than about 3% by weight of the RADARADARADARADA (SEQ. ID. NO. I) sequence. 
     
     
         41 . The method of  claim 38 , wherein the amphiphilic self-assembling peptide comprises a RADARADARADARADA (SEQ. ID NO. 1) sequence modified with one or more additional sequences. 
     
     
         42 . The method of  claim 38 , wherein the substantially cell free solution comprises a physiologically acceptable concentration of sucrose. 
     
     
         43 . The method of  claim 38 , wherein the substantially cell free solution comprises one or more of a growth factor and therapeutic agent. 
     
     
         44 . The method of  claim 1 , further comprising introducing a buffer to the substantially cell free solution to produce a buffered substantially cell free solution. 
     
     
         45 . The method of  claim 44 , wherein the substantially cell free solution comprises a pH of about 7 to about 8.5. 
     
     
         46 . The method of  claim 1 , wherein the therapeutically effective amount is about 50 μL. 
     
     
         47 . The method of  claim 1 , wherein the improvement of the infarcted myocardium is about 7% over about a 4-week time period as compared to a control solution.