Methods for treatment of bile acid-related disorders

Abstract

Provided herein are variants of fibroblast growth factor 19 (FGF19) proteins and peptide sequences (and peptidomimetics) and fusions of FGF19 and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), and variants of fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics). In some embodiments, these variants and fusions modulate bile acid homeostasis, and are useful in treatment of bile acid related and associated disorders. In some embodiments, these variants and fusions have glucose lowering activity, and are useful in treatment of hyperglycemia and other disorders.

1 .- 76 . (canceled) 
     
     
         77 . A method of preventing the induction or exacerbation of pruritus associated with non-alcoholic steatohepatitis (NASH) in a subject being treated for NASH, comprising administering to the subject an effective amount of a peptide, wherein the peptide comprises: 
       
         
           
                 
               
                   (SEQ ID NO: 70) 
                 
                   MRDSSPLVHYGWGDPIRLRHLYTSGPHGLSSCFLRIRADGVVDCARGQSA 
                 
                     
                 
                   HSLLEIKAVALRTVAIKGVHSVRYLCMGADGKMQGLLQYSEEDCAFEEEI 
                 
                     
                 
                   RPDGYNVYRSEKHRLPVSLSSAKQRQLYKNRGFLPLSHFLPMLPMVPEEP 
                 
                     
                 
                   EDLRGHLESDMFSSPLETDSMDPFGLVTGLEAVRSPSFEK (M70).  
                 
             
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         78 . The method of  claim 77 , wherein the peptide consists of SEQ ID NO:70. 
     
     
         79 . The method of  claim 77 , wherein the effective amount of the peptide is 0.3 mg. 
     
     
         80 . The method of  claim 77 , wherein the effective amount of the peptide is 1 mg. 
     
     
         81 . The method of  claim 77 , wherein the effective amount of the peptide is 2 mg. 
     
     
         82 . The method of  claim 77 , wherein the effective amount of the peptide is 3 mg. 
     
     
         83 . The method of  claim 77 , wherein the effective amount of the peptide is 5 mg. 
     
     
         84 . The method of  claim 77 , wherein the effective amount of the peptide is 10 mg. 
     
     
         85 . The method of  claim 77 , wherein the peptide is for administration once a day. 
     
     
         86 . The method of  claim 77 , wherein the peptide is for administration twice a day. 
     
     
         87 . The method of  claim 77 , wherein the peptide is for subcutaneous administration. 
     
     
         88 . The method of  claim 77 , wherein the peptide is for administration for 7 days or longer. 
     
     
         89 . The method of  claim 77 , wherein the peptide is for administration for 14 days or longer. 
     
     
         90 . The method of  claim 77 , wherein the peptide is for administration for 21 days or longer. 
     
     
         91 . The method of  claim 77 , wherein the peptide is for administration for 28 days or longer. 
     
     
         92 . The method of  claim 77 , wherein the peptide is for administration for 1 to 12 months. 
     
     
         93 . The method of  claim 77 , wherein the peptide is for administration for 12 months. 
     
     
         94 . The method of  claim 77 , wherein the peptide is for administration for more than 12 months. 
     
     
         95 . The method of  claim 77 , wherein the peptide is administered in combination with ursodeoxycholic acid (UDCA). 
     
     
         96 . The method of  claim 77 , wherein the subject is a human.