A new treatment approach involves blocking a protein – interleukin 11.
A team of researchers led by Duke-NUS Medical School and National Heart Centre Singapore (NHCS) found that deactivating a specific protein − interleukin 11 (IL11) – with drugs called therapeutic antibodies, reverses inflammation and scarring of the liver in patients suffering from an untreatable type of fatty liver disease called non-alcoholic steatohepatitis (NASH).
The findings were published in Gastroenterology, have implications for the development of drugs to treat the disease.
Fatty liver disease affects approximately one in four people around the world. People with diabetes and obesity are particularly at risk. Fatty liver disease can progress to cause liver inflammation, fibrosis and NASH, which increases the risk of liver failure. There is currently no treatment for fatty liver disease and NASH, and drugs tested in patients thus far have failed to work.
The team found that the IL11 gene triggers the development of NASH and fat accumulates in the livers of people with the condition. It is most common in people who are obese and diabetic, and causes fatigue, abdominal pain, itchy skin, nausea, and can ultimately lead to liver cirrhosis or cancer.
The therapeutic antibodies developed by Duke-NUS and NHCS researchers inhibited IL11 in a pre-clinical model that mimicked the human form of NASH, preventing and reversing liver inflammation, and even leading to lower blood levels of cholesterol and glucose.
“Millions of people are affected by diabetes and dangerous fatty liver disease. This new approach will not only treat these patients and restore their liver function, but also lower the dangerous fats and glucose in their blood,” added Professor Stuart Cook, corresponding author of the study, who is the Tanoto Foundation Professor in Cardiovascular Medicine and Director of the CVMD Programme at Duke-NUS, Senior Consultant at NHCS, and Director and Co-Founder of Enleofen Bio, a biotechnology company established in Singapore that is now developing the antibody therapeutics for clinical trials. The company aims to have the drugs ready for clinical trials by the end of 2020. [APBN]
Source: Widjaja AA, Singh BK, Adami E, Viswanathan S, Dong J, D’Agostino GA, Ng B, Lim WW, Tan J, Paleja BS, Tripathi M, Lim SY, Shekeran SG, Chothani SP, Rabes A, Sombetzki M, Bruinstroop E, Min LP, Sinha RA, Albani S, Yen PM, Schafer S and Cook SA (2019). Inhibiting Interleukin 11 Signaling Reduces Hepatocyte Death and Liver Fibrosis, Inflammation, and Steatosis in Mouse Models of Non-Alcoholic Steatohepatitis. Gastroenterology. DOI: 10.1053/j.gastro.2019.05.002