Compositions and Method for Treating Primary Sclerosing Cholangitis and Related Disorders

Abstract

The present disclosure is in the field of pharmaceutical compositions suitable for the treatment of diseases in mammals. The disclosure provides novel compositions comprising non-pathogenic fecal microbes for treating primary sclerosing cholangitis and related diseases. The disclosure also provides methods for treating a subject with the compositions disclosed herein.

1 . A method for treating primary sclerosing cholangitis in a human subject in need thereof, said method comprising orally administering to said human subject a pharmaceutically active dose of a therapeutic composition comprising viable non-pathogenic fecal bacteria or a non-cellular fecal filtrate. 
     
     
         2 . The method of  claim 1 , wherein said primary sclerosing cholangitis is selected from the group consisting of stage 1, stage 2, stage 3, and stage 4 primary sclerosing cholangitis. 
     
     
         3 . The method of  claim 1 , wherein said therapeutic composition comprises a non-selected fecal microbiota. 
     
     
         4 . The method of  claim 3 , wherein said fecal microbiota comprises a donor's entire fecal microbiota. 
     
     
         5 . The method of  claim 3 , wherein said fecal microbiota is from synthetic fecal material. 
     
     
         6 . The method of  claim 1 , wherein said method reduces the levels of disease indicators selected from the group comprising serum bilirubin, serum aminotransferase, alkaline phosphatase, gamma-glutamyltransferase (GGT), gamma globulin, IgM, serum alkaline phosphatase, or a combination thereof after at least 8 weeks of treatment. 
     
     
         7 . The method of  claim 1 , wherein said dose is administered at least once daily for at least 2 weeks. 
     
     
         8 . The method of  claim 1 , wherein said dose is administered at least twice weekly for at least two weeks. 
     
     
         9 . The method of  claim 8 , wherein said dose is administered at least twice weekly for at least 4 weeks. 
     
     
         10 . The method of  claim 8 , wherein said dose is administered at least twice weekly for at least 8 weeks. 
     
     
         11 . The method of  claim 1 , wherein said dose is administered at least three times weekly for at least 4 weeks. 
     
     
         12 . The method of  claim 1 , wherein said therapeutic composition comprises both live non-pathogenic fecal bacteria and a non-cellular fecal filtrate. 
     
     
         13 . The method of  claim 1 , wherein said method comprises a first dosing schedule followed by a second dosing schedule, wherein said second dosing schedule comprises a maintenance dose lower or equal to the dose of said first dosing schedule. 
     
     
         14 . The method of  claim 1 , wherein said therapeutic composition is formulated as a delayed or gradual enteric release form. 
     
     
         15 . The method of  claim 1 , wherein said therapeutic composition is formulated as an enteric coated capsule or an acid-resistant capsule. 
     
     
         16 . The method of  claim 1 , wherein said pharmaceutically active dose is from 10 8  to 10 14  cfu or total number of cells. 
     
     
         17 . The method of  claim 1 , wherein said therapeutic composition is in a liquid, frozen, freeze-dried, spray-dried, foam-dried, or powder form. 
     
     
         18 . The method of  claim 1 , wherein said therapeutic composition comprises a cryoprotectant selected from the group consisting of polyethylene glycol, skim milk, erythritol, arabitol, sorbitol, glucose, fructose, alanine, glycine, proline, sucrose, lactose, ribose, trehalose, dimethyl sulfoxide (DMSO), glycerol, and a combination thereof. 
     
     
         19 . The method of  claim 1 , wherein said subject is pretreated with an antibiotic prior to administration of said composition. 
     
     
         20 . The method of  claim 1 , wherein said method eliminates or reduces one or more symptoms selected from the group consisting of fatigue, itchiness, jaundice, inflammation of the bile ducts, fever, upper abdominal pain, impairment of bile secretion, easy bruising, greasy and foul-smelling stools, gallstones, bile duct stones, anemia, osteoporosis, cirrhosis of the liver, portal hypertension, ascites, liver failure, and cholangiocarcinoma. A method for maintaining treatment efficacy in a subject in need thereof, said method comprising administering to said subject a pharmaceutically active dose of a composition comprising live non-pathogenic fecal bacteria or a non-cellular fecal filtrate.