The therapy under preclinical investigation is an inhibiting interleukin 11 (IL11) antibody treatment that addresses multiple aspects of non-alcoholic steatohepatitis (NASH), including hepatic inflammation and fibrosis. The study was led by Enleofen's co-founders, Professor Stuart Cook and Assistant Professor Sebastian Schafer, and conducted with an international team of scientists at Duke-NUS Medical School (Duke-NUS) and National Heart Centre Singapore (NHCS).
The data from this preclinical study suggests that Enleofen's IL11 signal inhibition strategy could be effective in treating this common but currently incurable type of liver disease even at an advanced stage, said Dr. Stuart Cook.
The researchers discovered that IL11 was elevated in the livers of NASH patients. Further studies showed conclusively that liver cells start to produce IL11 as soon as the liver is loaded with fat. IL11 then triggers hepatocyte damage and promotes inflammation and fibrosis. Antibodies neutralising IL11 signalling were administered to several preclinical models of NASH and effectively blocked this vicious disease cycle, which resulted in strong therapeutic effects. Turning off scarring of the liver is very difficult to achieve and is one of the highlights of the novel therapy.
The study also showed that as the liver recovered, the overall metabolic profile also improved as indicated by lowered blood cholesterol and glucose during treatment. This highlights the central importance of the liver for metabolic disease and suggests Enleofen's therapies may provide a holistic approach for treating multiple aspects of ill health in diabetic and obese individuals with liver disease.
IL11 has been overlooked as a therapeutic target, but we found that it is the central player of this liver disease, added Dr. Sebastian Schafer. We look forward to validating this strategy in a Phase 1 clinical trial.
Fatty liver disease affects one in four people around the world and is most common in obese and diabetic people. It can progress to NASH, which is characterised by liver inflammation, fibrosis and an increased risk of liver failure. NASH causes fatigue, abdominal pain, itchy skin, nausea, and can ultimately lead to liver cirrhosis or cancer. There are currently no approved treatments for NASH.