Abstract: The present invention derives from the unexpected finding that pyroptosis is a novel biomarker and target for therapy in liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Gasdermin D (GSDMD), caspase 4, caspase 5, or Interleukin 1 alpha (IL-1?) can be detected and quantified in serum or plasma, and used as biomarkers for outcome in liver failure such as acute liver failure (ALF) and ACLF and other diseases involving aberrant pyroptosis. By antagonising GSDMD, caspase 4, caspase 5 or Interleukin 1 alpha (IL-1?) many of the unwanted consequences or symptoms of liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of GSDMD, caspase 4, caspase 5 or IL-1? that may be used in the treatment or prevention of liver failure such as acute liver failure (ALF) and ACLF.

Abstract: The present invention derives from the unexpected finding that pyroptosis is a novel biomarker and target for therapy in liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Gasdermin D (GSDMD), caspase 4, caspase 5, or Interleukin 1 alpha (IL-1?) can be detected and quantified in serum or plasma, and used as biomarkers for outcome in liver failure such as acute liver failure (ALF) and ACLF and other diseases involving aberrant pyroptosis. By antagonising GSDMD, caspase 4, caspase 5 or Interleukin 1 alpha (IL-1?) many of the unwanted consequences or symptoms of liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of GSDMD, caspase 4, caspase 5 or IL-1? that may be used in the treatment or prevention of liver failure such as acute liver failure (ALF) and ACLF.

Abstract: The present invention derives from the finding that expression of DDAH1 is heavily post-transcriptionally regulated by microRNAs. By preventing or blocking the interaction between such microRNAs and the DDAH1 mRNA, the production of DDAH1 protein can be increased. This has utility in the prevention or treatment of diseases and disorders that are associated with reduced DDAH1 levels or increased ADMA levels, such as diseases or disorders that are characterised by endothelial dysfunction.

Abstract: The present invention derives from the finding that decreased levels of DDAH I are associated with increased portal pressure and that by increasing DDAH I levels in vivo, portal pressure may be reduced. Accordingly, the invention provides methods for reducing portal blood pressure comprising administering to a subject in need thereof an agonist of DDAH I.