Modulators of hsd17b13 expression

Abstract

Methods, compounds, and compositions useful for inhibiting HSD expression are provided. Such compounds, compositions, and methods are useful for treating, preventing, or ameliorating a disease associated with HSD 17B 13.

1 - 108 . (canceled) 
     
     
         109 . An oligomeric compound, according to the following chemical structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         110 . An oligomeric compound, according to the following chemical structure: 
       
         
           
           
               
               
           
         
       
     
     
         111 . An oligomeric compound comprising a modified oligonucleotide consisting of 16 linked nucleosides having a nucleobase sequence SEQ ID NO: 1448, wherein the modified oligonucleotide comprises
 a gap segment consisting of ten linked deoxynucleosides;   a 5′ wing segment consisting of three linked nucleosides; and   a 3′ wing segment consisting of three linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein the 5′ wing segment and the 3′ wing segment comprise cEt sugars; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine.   
     
     
         112 . The oligomeric compound of  claim 109 , which is a sodium salt or a potassium salt. 
     
     
         113 . A pharmaceutical composition comprising the oligomeric compound of any one of  claims 109 - 112  and a pharmaceutically acceptable diluent. 
     
     
         114 . The pharmaceutical composition of  claim 113 , wherein the pharmaceutically acceptable diluent is water. 
     
     
         115 . A method of treating a disease associated with HSD17B13 in an individual comprising administering to the individual a compound of any one of  claims 109 - 112 , thereby treating the disease. 
     
     
         116 . The method of  claim 115 , wherein the individual has a liver disease, NAFLD, NASH, alcoholic steatohepatitis (ASH), alcoholic liver disease, nonalcoholic liver disease, alcoholic cirrhosis, nonalcoholic cirrhosis, steatohepatisis, hepatic steatosis, hepatocellular carcinoma, alcoholic liver disease, HCV hepatitis, chronic hepatitis, hereditary hemochromatosis, or primary sclerosing cholangitis. 
     
     
         117 . A method of inhibiting expression of HSD17B13 in a cell comprising contacting the cell with an oligomeric compound of any one of  claims 109 - 112 , thereby inhibiting expression of HSD17B13 in the cell. 
     
     
         118 . The method of  claim 117 , wherein the cell is in the liver of an individual. 
     
     
         119 . The method of  claim 118 , wherein the individual has, or is at risk of having, liver disease, NAFLD, NASH, alcoholic steatohepatitis (ASH), alcoholic liver disease, nonalcoholic liver disease, alcoholic cirrhosis, nonalcoholic cirrhosis, steatohepatisis, hepatic steatosis, hepatocellular carcinoma, alcoholic liver disease, HCV hepatitis, chronic hepatitis, hereditary hemochromatosis, or primary sclerosing cholangitis. 
     
     
         120 . A method of ameliorating liver damage, steatosis, liver fibrosis, liver inflammation, liver scarring or cirrhosis, liver failure, liver enlargement, elevated transaminases, or hepatic fat accumulation in an individual, comprising administering an oligomeric compound of any one of  claims 109 - 112  to the individual, thereby ameliorating liver damage, steatosis, liver fibrosis, liver inflammation, liver scarring or cirrhosis, liver failure, liver enlargement, elevated transaminases, or hepatic fat accumulation in the individual. 
     
     
         121 . The method of  claim 120 , wherein the individual has, or is at risk of having, liver disease, NAFLD, NASH, alcoholic steatohepatitis (ASH), alcoholic liver disease, nonalcoholic liver disease, alcoholic cirrhosis, nonalcoholic cirrhosis, steatohepatisis, hepatic steatosis, hepatocellular carcinoma, alcoholic liver disease, HCV hepatitis, chronic hepatitis, hereditary hemochromatosis, or primary sclerosing cholangitis.