Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat is stored in the liver. This build-up of fat is not caused by heavy alcohol use. Two types of NAFLD are simple fatty liver and non-alcoholic steatohepatitis (NASH). Simple fatty liver and NASH are two separate conditions, and people typically develop one or the other. NASH is characterized by inflammation of the liver (hepatitis) and liver cell damage. Inflammation and liver cell damage can cause scarring (fibrosis) of the liver leading to cirrhosis. NASH may lead to other complications such as decompensated cirrhosis of the liver, in which the liver no longer functions, and liver cancer.
Selonsertib is an investigational oral small molecule inhibitor of ASK1, a protein that mediates inflammation, apoptosis (cell death) and fibrosis in settings of oxidative stress. Oxidative stress can be increased in many pathological conditions including liver diseases such as NASH. NASH currently has no effective treatment apart from lifestyle interventions. If licensed, selonsertib will offer a new treatment option for NASH as no effective pharmacological therapies currently exist.
Timolumab is currently being developed to treat PSC. Timolumab is given by injection into the vein which blocks a molecule called VAP-1 from working. VAP-1 helps immune cells enter areas of inflammation (such as the bile ducts in PSC) where they can further contribute to inflammation. By blocking this process, timolumab has the potential to prevent some of the inflammation in PSC and slow the progress of the disease.