Methods for treatment of diseases

Abstract

We describe peptides and their uses for the treatment of , e.g. acute myocardial infarction and other cytokine storm-associated conditions.

1 . A method of treating a disease associated with a cytokine storm, comprising administering to a human subject affected with the disease a pharmaceutical composition comprising a peptide selected from the group consisting of:
 (a) a peptide comprising the amino acid sequence   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   VKFNKPFVFLMIEQNTK; 
                 
             
                
                
               
            
           
         
         (b) a peptide consisting essentially of the amino acid sequence 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 4) 
                 
                     
                   RFNRPFLR. 
                 
             
                
                
               
            
           
         
         (c) a peptide consisting essentially of the amino acid sequence of 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 8) 
                 
                     
                   RRRFNRPFLRRR. 
                 
             
                
                
               
            
           
         
         (d) a peptide consisting essentially of the amino acid sequence of 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   VKFNKPFVFLMIEQNTK; 
                 
             
                
                
               
            
           
         
         (e) a peptide consisting essentially of the amino acid sequence of 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 10) 
                 
                     
                   FNRPFL; 
                 
             
                
                
               
            
           
         
         (f) a peptide comprising 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 57) 
                 
                     
                     VKFNKPFVFL[Nle]IEQNTK . 
                 
             
                
                
               
            
           
         
         wherein the peptide has a size of 35 amino acids or less. 
       
     
     
         2 . The method of  claim 1 , wherein the disease associated with a cytokine storm is selected from the group consisting of:
 acute myocardial infarction (AMI); gout; stroke; heart surgery complications; and traumatic brain injury.   
     
     
         3 . A method of reducing infarct size in a human subject in need of treatment therefor, comprising administering to the human subject a pharmaceutical composition comprising a peptide selected from the group consisting of:
 (a) a peptide comprising the amino acid sequence   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   VKFNKPFVFLMIEQNTK; 
                 
             
                
                
               
            
           
         
         (b) a peptide consisting essentially of the amino acid 
       
       
         
           
                 
                 
               
                     
                   sequence 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   RFNRPFLR. 
                 
             
                
                
                
               
            
           
         
         (c) a peptide consisting essentially of the amino acid sequence of 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 8) 
                 
                     
                   RRRFNRPFLRRR. 
                 
             
                
                
               
            
           
         
         (d) a peptide consisting essentially of the amino acid sequence of 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   VKFNKPFVFLMIEQNTK; 
                 
             
                
                
               
            
           
         
         (e) a peptide consisting essentially of the amino acid sequence of FNRPFL (SEQ ID NO: 10); and 
         (f) a peptide comprising 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 57) 
                 
                     
                     VKFNKPFVFL[Nle]IEQNTK . 
                 
             
                
                
               
            
           
         
       
       wherein the peptide has a size of 35 amino acids or less. 
     
     
         4 . The method of  claim 3 , wherein the human subject in need of a reduction in infarct size is a subject in need of treatment for a disease selected from the group consisting of:
 acute myocardial infarction (AMI); ischemia; stroke; traumatic brain injury; and toxic shock.   
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutical composition is administered orally or subcutaneously to the human subject. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical composition further comprises at least one second peptide or protein attached to the peptide to form a fusion protein. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 7 , wherein the at least one second peptide or protein is an epitope tag or a half-life extender or both. 
     
     
         10 . The method of  claim 1 , wherein the peptide comprises one or more D-amino acids. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the peptide consists of 22 amino acid residues, 21 amino acid residues, or fewer. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 3 , wherein the pharmaceutical composition is administered orally or subcutaneously to the human subject. 
     
     
         18 . The method of  claim 3 , wherein the pharmaceutical composition further comprises at least one second peptide or protein attached to the peptide to form a fusion protein. 
     
     
         19 . The method of  claim 18 , wherein the at least one second peptide or protein is an epitope tag or a half-life extender or both. 
     
     
         20 . The method of  claim 3 , wherein the peptide comprises one or more D-amino acids. 
     
     
         21 . The method of  claim 3 , wherein the peptide consists of 22 amino acid residues, 21 amino acid residues, or fewer. 
     
     
         22 . A pharmaceutical composition comprising a peptide comprising the amino acid sequence of VKFNKPFVFL[Nle]IEQNTK (SEQ ID NO: 57), and a pharmaceutically acceptable carrier, wherein the peptide has a size of 35 amino acids or less. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein the peptide consists of 22 amino acid residues, 21 amino acid residues, or fewer. 
     
     
         24 . The pharmaceutical composition of  claim 22 , wherein the composition is formulated into a dosage form suitable for oral, parenteral, intraperitoneal, rectal, subcutaneous, nasal, vaginal, inhalant, dermal, or ocular administration. 
     
     
         25 . The pharmaceutical composition of  claim 22 , wherein the peptide is fused to an epitope tag, or a half-life extender. 
     
     
         26 . The pharmaceutical composition of  claim 22 , wherein the peptide is modified by PEGylation. 
     
     
         27 . The pharmaceutical composition of  claim 22 , wherein the N-terminus of the peptide is acetylated, the C-terminus of the peptide is amidated, or both.