Extracelluar matrix (ECM) remodelling is one of the key hallmarks promoting tissue fibrosis.
Excess ECM leads to pathological fibrosis.
Fibrosis is a pathological feature of many diseases that occurs as a result of inflammation or damage. Excessive collagen and other extracellular matrix (ECM) proteins accumulate in tissues, impairing their physiological function. Fibrosis can occur in almost any tissue and can eventually result in scarring of affected organs, leading to irreparable damage and ultimately organ failure. It has been estimated that fibrosis is prevalent in 45% of all diseases. There are no approved drugs to treat it. Fibrosis therefore represents a huge unmet clinical need.
A better understanding of how the ECM regulates organ structure and function and of how ECM remodeling affects disease progression could contribute to the development of new therapeutics.
of deaths in the USA attributed to fibrotic disorders
Wynn. TA. 2008. Cellular and molecular mechanisms of fibrosis. The Journal of Pathology. 214(2): 199-210.
Bonnans C et al. 2015. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15, 786–801.
Primary Sclerosing Cholangitis – Engitix lead programme
Primary sclerosing cholangitis (PSC) is a rare, persistent and progressive fibrotic disease of the liver, characterised by inflammation and scarring of the bile ducts. The cause and pathogenesis of PSC are unclear, but thought that both genetic and environmental risk factors contribute to its development and progression. PSC frequently occurs in the setting of inflammatory bowel disease.
Urgent need – the facts
There are limited therapeutic options and a liver transplant is the only effective therapy to date with only a few drugs in clinical development.
patients ultimately will need liver transplantation
estimated patients in USA and Europe
Recurrence of PSC in patients after liver transplantation
Using our unique in vitro models based on ECM from PSC livers combined with our expertise in ECM-driven biology we are discovering target and biomarkers as well as carrying out drug profiling.
Non-alcoholic steatohepatitis – programme partnered with Takeda Pharmaceuticals
Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD). NASH is caused by a build-up of fat in the liver which leads to inflammation and damage, resulting in scarring of the liver, and cirrhosis which is a potentially life-threatening.
There are currently no approved medicines for NASH.
of the world’s population are affected by NASH
Estes. C, et al. 2018. Modeling the epidemic of non-alcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 67(1):123-133.
Estes. C, et al. 2018. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. Journal of Hepatology. 69(4): 896-904.
Inflammatory bowel disease – programme partnered with Takeda Pharmaceuticals
Inflammatory bowel disease (IBD) is an umbrella term describing chronic conditions that involve inflammation of the digestive tract, including ulcerative colitis and Crohn’s disease (CD).
Fibrostenotic CD patients in particular have high disease burden; stricture-induced intestinal obstruction is the most common indication for surgery within CD, with up to 70% of fibrostenotic CD patients requiring multiple surgical procedures. There is currently no clinical treatment for intestinal fibrosis pathology in IBDs.
of Crohn’s disease patients need surgery