Use of glp-1 receptor agonists for the treatment of gastrointestinal disorders

Abstract

The present invention describes the methods of using incretin mimetics such as GLP-1 receptor agonists, particularly exenatide, to treat short bowel syndrome and spastic or hyperactive esophageal motor disorders.

1 . A method for treating spastic or hyperactive esophageal motor disorder in a subject in need thereof, comprising:
 providing an incretin mimetic; and   administering a therapeutically effective amount of the incretin mimetic to the subject to treat the spastic or hyperactive esophageal motor disorder.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the spastic or hyperactive esophageal motor disorder is selected from the group consisting of esophageal spasm, nutcracker esophagus, achalasia and combinations thereof. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the incretin mimetic is a glucagon-like peptide-1 (GLP-1) receptor agonist. 
     
     
         6 . The method of  claim 5 , wherein the GLP-1 receptor agonist is an exendin. 
     
     
         7 . The method of  claim 6 , wherein the exendin is exendin-3, exendin-4, or functional derivatives thereof. 
     
     
         8 . The method of  claim 6 , wherein the exendin is exenatide. 
     
     
         9 . The method of  claim 5 , wherein the GLP-1 receptor agonist is GLP-1 or a biologically active form of GLP-1. 
     
     
         10 . The method of  claim 5 , wherein the GLP-1 receptor agonist is a purified polypeptide having an amino acid sequence at least 95% identical to SEQ ID NO: 1. 
     
     
         11 . The method of  claim 5 , wherein the GLP-1 receptor agonist is a purified polypeptide as disclosed by SEQ ID NO: 1 with up to five conservative amino acid substitutions. 
     
     
         12 . The method of  claim 1 , wherein the therapeutically effective amount is about 5 micrograms (mcg) to about 10 mcg. 
     
     
         13 . The method of  claim 1 , wherein administering comprises administering the therapeutically effective amount twice per day. 
     
     
         14 . A method of normalizing bowel function in a subject in need thereof, comprising:
 providing an incretin mimetic; and   administering a therapeutically effective amount of the incretin mimetic to the subject.   
     
     
         15 . The method of  claim 14 , wherein normalizing bowel function comprises reducing the number of bowel movements in the subject. 
     
     
         16 . The method of  claim 14 , wherein the incretin mimetic is a glucagon-like peptide-1 (GLP-1) receptor agonist. 
     
     
         17 . The method of  claim 16 , wherein the GLP-1 receptor agonist is an exendin. 
     
     
         18 . The method of  claim 17 , wherein the exendin is exendin-3, exendin-4, or functional derivatives thereof. 
     
     
         19 . The method of  claim 17 , wherein the exendin is exenatide. 
     
     
         20 . The method of  claim 16 , wherein the GLP-1 receptor agonist is GLP-1 or a biologically active form of GLP-1. 
     
     
         21 . The method of  claim 16 , wherein the GLP-1 receptor agonist is a purified polypeptide having an amino acid sequence at least 95% identical to SEQ ID NO: 1. 
     
     
         22 . The method of  claim 16 , wherein the GLP-1 receptor agonist is a purified polypeptide as disclosed by SEQ ID NO: 1 with up to five conservative amino acid substitutions. 
     
     
         23 . The method of  claim 14 , wherein the therapeutically effective amount is about 5 micrograms (mcg) to about 10 mcg. 
     
     
         24 . The method of  claim 14 , wherein administering comprises administering the therapeutically effective amount twice per day. 
     
     
         25 . A kit for treating a gastrointestinal disorder in a subject in need thereof, comprising:
 an incretin mimetic; and   instructions to administer a therapeutically effective amount of the incretin mimetic to the subject.   
     
     
         26 . The kit of  claim 25 , wherein the incretin mimetic is a glucagon-like peptide-1 (GLP-1) receptor agonist. 
     
     
         27 . The kit of  claim 25 , wherein the gastrointestinal disorder is selected from the group consisting of short bowel syndrome, spastic or hyperactive esophageal motor disorder and combinations thereof. 
     
     
         28 . The kit of  claim 26 , wherein the GLP-1 receptor agonist is exenatide.