Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders
AssigneeNGM Biopharmaceuticals, Inc.
InventorsAlexander Mark Depaoli, Jian Luo, Hui Tian
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Abstract
Provided herein are methods of using 7α-hydroxy-4-cholesten-3-one (C4) in predicting the clinical sensitivity to treatment of bile acid-related and associated disorders with treatment peptides, such as 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).
Claims10
A method of selectively treating a subject having or suspected of having a bile acid-related disorder comprising administering to the subject a peptide having an amino acid sequence comprising SEQ ID NO:70, wherein the subject has been determined to be likely to responsive to the peptide according a method comprising:
- (a) administering the peptide to the subject;
- (b) obtaining a test sample from the subject;
- (c) determining the level of 7α-hydroxy-4-cholesten-3-one (C4) in the test sample;
- and
- (d) identifying the subject as being likely to be responsive to treatment with the peptide if the level of C4 in the test sample decreases as compared to a reference level of C4,
- wherein the bile-acid related disorder comprises a metabolic syndrome, a lipid or glucose disorder, cholesterol or triglyceride metabolism, type 2 diabetes, cholestasis, intrahepatic cholestasis, primary biliary cirrhosis (PBC), primary familial intrahepatic cholestasis (PFIC), progressive PFIC, primary sclerosing cholangitis (PSC), pregnancy intrahepatic cholestasis (PIC), neonatal cholestasis, drug induced cholestasis, diseases of extrahepatic cholestasis, bile duct compression from tumor, bile duct blockade by gall stones, bile acid malabsorption, disorders involving the distal small intestine, ileal resection, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, idiopathic disorders impairing absorption of bile acids, diarrhea, bile acid diarrhea (BAD), GI symptoms, GI cancers, liver cancers, biliary cancers, colon cancer, hepatocellular cancer, bile acid synthesis abnormalities, cirrhosis, portal hypertension, or any combination thereof.
Dependencies are inferred from the claim text.