Peptide antagonists of zonulin and methods for use of the same

Abstract

Peptide antagonists of zonulin are disclosed, as well as methods for the use of the same. The peptide antagonists bind to the zonula occludens receptor, yet do not physiologically modulate the opening of mammalian tight junctions.

What is claimed is: 
     
         1 . A method for treatment of a condition associated with breakdown of the blood brain barrier comprising administering to a subject in need of such treatment, a pharmaceutically effective amount of a peptide antagonist of zonulin, wherein the peptide antagonist comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24 and SEQ ID NO:35; and wherein the peptide antagonist binds to a  zonula occludens  toxin receptor, yet does not physiologically modulate the opening of mammalian tight junctions. 
     
     
         2 . The method of  claim 1 , wherein the  zonula occludens  toxin receptor is in brain tissue. 
     
     
         3 . The method of  claim 1 , wherein the peptide competitively inhibits  zonula occludens  toxin (ZOT) and zonulin from binding to the  zonula occludens  toxin receptor and from modulating the opening of the mammalian tight junction. 
     
     
         4 . The method of  claim 1 , wherein the condition is cerebral ischemia. 
     
     
         5 . The method of  claim 1 , wherein the condition is stroke or cerebral edema. 
     
     
         6 . The method of  claim 1 , wherein the condition is hypertension. 
     
     
         7 . The method of  claim 1 , wherein the condition is convulsive seizure. 
     
     
         8 . The method of  claim 1 , wherein the condition is uremia. 
     
     
         9 . The method of  claim 1 , wherein the condition is meningitis. 
     
     
         10 . The method of  claim 1 , wherein the condition is encephalitis. 
     
     
         11 . The method of  claim 1 , wherein the condition is encephalomyelitis. 
     
     
         12 . The method of  claim 1 , wherein the condition is traumatic brain injury. 
     
     
         13 . The method of  claim 1 , wherein the condition is radiation brain injury. 
     
     
         14 . The method of  claim 1 , wherein the condition is multiple sclerosis. 
     
     
         15 . The method of  claim 1 , wherein the condition is Guillain-Barre Syndrome. 
     
     
         16 . A peptide antagonist of zonulin comprising an amino acid sequence selected from the group consisting of SEQ ID NO:6, SEQ ID NO:11, SEQ ID NO:15, and SEQ ID NO:23; and wherein said peptide antagonist binds to a  zonula occludens  toxin receptor, yet does not physiologically modulate the opening of mammalian tight junctions. 
     
     
         17 . A method for treatment of gastrointestinal inflammation comprising administering to a subject in need of such treatment, a pharmaceutically effective amount of a peptide antagonist of zonulin, wherein said peptide antagonist of zonulin comprises an amino acid sequence selected from the group consisting of SEQ ID NO:6, SEQ ID NO:11, SEQ ID NO:15 and SEQ ID NO:23, wherein said peptide antagonist binds to a  zonula occludens  toxin receptor in the intestine of said subject, yet does not physiologically modulate the opening of mammalian tight junctions in said intestine.