Method and use of peptide antagonists of zonulin to prevent or delay the onset of diabetes

Abstract

A method for preventing or delaying the onset of autoimmune diseases is disclosed.

1 . A method for prevention or delay of onset of an autoimmune disease, comprising: administering a pharmaceutically effective amount of a peptide antagonist of zonulin to a subject at risk of developing the autoimmune disease, wherein the peptide antagonist binds to zonula occludens toxin receptor but does not physiologically modulate the opening of mammalian intestinal tight junctions. 
     
     
         2 . The method of  claim 1 , 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, and SEQ ID NO: 24. 
     
     
         3 . The method of  claim 1 , wherein the peptide antagonist is from 8-110 amino acids in size. 
     
     
         4 . The method of  claim 1 , wherein the peptide antagonist is from 8-40 amino acids in size. 
     
     
         5 . The method of  claim 1 , wherein the peptide antagonist comprises amino acid sequence SEQ ID NO: 15. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the peptide antagonist is administered as an oral dosage composition for intestinal delivery. 
     
     
         8 . (canceled) 
     
     
         9 . A method for prevention or delay of onset of an autoimmune disease, comprising: administering a pharmaceutically effective amount of an antagonist of zonulin to a subject at risk of developing the autoimmune disease, wherein the antagonist binds to zonula occludens toxin receptor but does not physiologically modulate the opening of mammalian intestinal tight junctions. 
     
     
         10 . The method of  claim 9 , wherein the 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, and SEQ ID NO: 24. 
     
     
         11 . The method of  claim 9 , wherein the antagonist comprises a peptide comprising 8-110 amino acids. 
     
     
         12 . The method of  claim 9 , wherein the antagonist comprises a peptide comprising 8-40 amino acids. 
     
     
         13 . The method of  claim 9 , wherein the antagonist comprises amino acid sequence SEQ ID NO: 15. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 9 , wherein the antagonist is administered as an oral dosage composition for intestinal delivery. 
     
     
         16 . (canceled) 
     
     
         17 . A method for prevention of diabetes, comprising: administering to a subject in need of such prevention, a pharmaceutically effective amount of a peptide antagonist of zonulin, wherein the peptide antagonist binds to zonula occludens toxin receptor but does not physiologically modulate the opening of mammalian intestinal tight junctions. 
     
     
         18 . The method of  claim 17 , 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, and SEQ ID NO: 24. 
     
     
         19 . The method of  claim 17 , wherein the peptide antagonist is from 8-110 amino acids in size. 
     
     
         20 . The method of  claim 17 , wherein the peptide antagonist is from 8-40 amino acids in size. 
     
     
         21 . The method of  claim 17 , wherein the peptide antagonist comprises amino acid sequence SEQ ID NO: 15. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 17 , wherein the peptide antagonist is administered as an oral dosage composition for intestinal delivery. 
     
     
         24 - 32 . (canceled)