Ucl Business Plc

Yaqrit Limited

Other

Ocera Therapeutics, Inc.

University of Brighton

Hepyx Limited

Rajiv Jalan

Rajeshwar Prosad Mookerjee

Fausto Andreola

Nathan Davies

Krista Rombouts

Francesco De Chiara

Kamal Nayan Jalan

Karen Louise Thomsen

Naina Shah

Keith Anderson

Susan Rachel Sandeman

Sergey Victorovich Mikhalovsky

Carol Angela Howell

Jane MacNaughtan

Vanessa Stadlbauer

Takayuki Kondo

Stewart MacDonald

Gautam Mehta

Nigel Beaton

Ugo Soffientini

Cornelius Engelmann

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&#x3b1;) 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&#x3b1;) 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&#x3b1; that may be used in the treatment or prevention of liver failure such as acute liver failure (ALF) and ACLF. The present invention utilises these findings to identify and provide antagonists of GSDMD, caspase 4, caspase 5 or IL-1&#x3b1; that may be used in the treatment or prevention of aberrant pyroptosis in the kidney, brain, liver or other organ of the body.

Treatment of pyroptosis

The present invention derives from the unexpected finding that necroptosis is a novel biomarker and target for therapy in patients with liver failure such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). RIPK1, MLKL or RIPK3 can be detected and quantified in serum or plasma, and used as a biomarker for outcome in ACLF and other diseases involving aberrant necroptosis. By antagonising RIPK1, MLKL or RIPK3 many of the unwanted consequences or symptoms of acute-on-chronic liver failure (ACLF) may be reduced. The present invention utilises these findings to identify and provide antagonists of RIPK1, MLKL and RIPK3 that may be used in the treatment or prevention of ACLF. The present invention utilises these findings to identify and provide antagonists of RIPK1, MLKL or RIPK3 that may be used in the treatment or prevention of aberrant necroptosis in the kidney, brain, liver or other organ of the body.

Treatment of necroptosis

Disclosed herein are methods of treating and/or preventing portal hypertension and/or restoring liver function using L-ornithine phenylacetate.

Treatment of portal hypertension and restoration of liver function using L-ornithine phenylacetate

Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.

Treatment of diseases associated with hepatic stellate cell activation using ammonia-lowering therapies

The present invention derives from the finding that increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction and that by decreasing TLR4 levels in vivo, the kidney and brain consequences of liver disease that are precipitated by superimposed infection or inflammation may be reduced. Accordingly, the invention provides TLR4 antagonists for use in a method of treating an individual suffering from liver disease presenting with renal or brain dysfunction.

Treating hyperammonemia, reducing plasma ammonia with TLR4 antagonists

The present invention relates to use of ornithine in the manufacture of a medicament for use in combination with at least one of phenylacetate and phenylbutyrate for preventing or treating liver decompensation or hepatic encephalopathy. The invention also relates to use of at least one of phenylacetate and phenylbutyrate in the manufacture of a medicament for use in combination with ornithine for preventing or treating liver decompensation or hepatic encephalopathy.

Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy

Treating renal and liver dysfunction with TLR4 antagonists

The invention provides porous carbon particles for use in the treatment or prevention of liver disease, wherein at least 20% of the total pore volume is made up of pores having a mean diameter of from 2 to 200 nm and/or wherein the particles comprise micropores of diameter 2 nm or less and small macropores of diameter 50 nm to 500 nm, but substantially no mesopores of diameter greater than 2 nm and less than 50 nm, and substantially no large macropores of diameter greater than 500 nm.

Porous carbon particles for use in the treatment or prevention of liver disease

The invention provides an apparatus for use in the treatment of an individual suffering from liver disease, including: (a) means for selectively removing albumin from the blood of the individual; and (b) means for selectively removing endotoxin from the blood of the individual.

Therapy for liver disease

A method for assessing liver function in an individual, which method comprises determining the level of methylarginine(s) (such as ADMA and/or SDMA) and the ratio of ischemia modified albumin (IMA): albumin ratio (IMAR) in the individual, thereby to assess liver function in the individual.

Biomarkers for assessing liver function

A method for assessing prognosis in an individual suffering from liver failure, which method comprises detecting endotoxin in the individual, for example by determining the neutrophil function in the individual. The method can be used to determine whether there is an increased risk of infection in the individual, an increased risk of organ failure in the individual, an increased risk of mortality in the individual and/or an increased risk that the individual will not respond positively to treatment with an immunosuppressive agent, a steroid or an antibiotic.

Growing community of inventors

London, United Kingdom

Rajiv Jalan