US2013157943A1PendingUtilityA1

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

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Assignee: FASANO ALESSIOPriority: May 19, 2000Filed: May 1, 2012Published: Jun 20, 2013
Est. expiryMay 19, 2020(expired)· nominal 20-yr term from priority
Inventors:Alessio FasanoTammara L. Watts
A61P 3/10A61K 38/00A61P 1/14C07K 7/06Y10S530/844C07K 14/4705
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Claims

Abstract

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

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         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 . The method of  claim 1 , wherein the peptide antagonist consists of amino acid sequence SEQ ID NO: 15. 
     
     
         7 . The method of  claim 1 , wherein the peptide antagonist is administered as an oral dosage composition for intestinal delivery. 
     
     
         8 . The method of  claim 1 , wherein the peptide antagonist consists of 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. 
     
     
         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 . The method of  claim 9 , wherein the antagonist consists of amino acid sequence SEQ ID NO: 15. 
     
     
         15 . The method of  claim 9 , wherein the antagonist is administered as an oral dosage composition for intestinal delivery. 
     
     
         16 . The method of  claim 9 , wherein the antagonist comprises a peptide, wherein the peptide consists of 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. 
     
     
         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 . The method of  claim 17 , wherein the peptide antagonist consists of amino acid sequence SEQ ID NO: 15. 
     
     
         23 . The method of  claim 17 , wherein the peptide antagonist is administered as an oral dosage composition for intestinal delivery. 
     
     
         24 . The method of  claim 17 , wherein the peptide antagonist consists of 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. 
     
     
         25 . A method for prevention or delay of onset of diabetes, comprising:
 administering a pharmaceutical effective amount of an antagonist of zonulin to a subject at risk of developing diabetes, wherein the antagonist binds to zonula occludens toxin receptor but does not physiologically modulate the opening of mammalian intestinal tight junctions.   
     
     
         26 . The method of  claim 25 , 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. 
     
     
         27 . The method of  claim 25 , wherein the antagonist comprises a peptide comprising 8-110 amino acids. 
     
     
         28 . The method of  claim 25 , wherein the antagonist comprises a peptide comprising 8-40 amino acids. 
     
     
         29 . The method of  claim 25 , wherein the antagonist comprises amino acid sequence SEQ ID NO: 15. 
     
     
         30 . The method of  claim 25 , wherein the antagonist consists of amino acid sequence SEQ ID NO: 15. 
     
     
         31 . The method of  claim 25 , wherein the antagonist is administered as an oral dosage composition for intestinal delivery. 
     
     
         32 . The method of  claim 25 , wherein the antagonist comprises a peptide, wherein the peptide consists of 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.

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