“Meer kennis met minder dieren” (ZonMw) grant for Olinga

A team of researchers from the Groningen Research Institute of Pharmacy (Prof Dr E.M.J. Verpoorte and Prof Dr Peter Olinga), University of Mainz (Prof Dr Dr D. Schuppan), and Boehringer Ingelheim has recently been awarded a grant for 625 k€ within the program ‘Meer Kennis met Minder Dieren’. This research is financially supported by both ZonMW and Proefdiervrij and led by Olinga (Pharmaceutical Technology and Biopharmacy group of GRIP).

Human ex vivo model to study nonalcoholic fatty liver disease and its associated pathologies
Obesity is closely associated with insulin resistance and nonalcoholic fatty liver (NAFL). Steatosis, the accumulation of fat in the liver is a main feature of NAFL, which occurs when the rate of hepatic fatty acid uptake and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and excretion via lipoproteins . NAFL affects up to one third of the population in developed and developing countries. Moreover, in one out of 6 patients with NAFL the disease progresses to non-alcoholic steatohepatitis (NASH), which is characterized by hepatocyte apoptosis, hepatic inflammation, fibrosis, and a risk of progression to cirrhosis, liver failure and primary liver cancer. NASH also dramatically increases the risk of overt type 2 diabetes and cardiovascular morbidity and mortality. NASH has become a leading cause of liver cirrhosis and liver cancer. Life style changes on their own are generally not sufficient to effectively treat established NASH . Thus there is an urgent need for effective pharmacological therapy that addresses both the liver disease and the associated metabolic comorbidities.

Currently, long-term dietary models, or genetic models with little resemblance to the multifactorial human etiology, are utilized in NAFL/NASH research. These animal models are associated with high discomfort for the animals studied, and show only 1-12% overlap in the disease related transcriptome. No model replicates the full spectrum of the progression of NAFL to fibrosis and cancer. Such species differences, a common denominator in animal research, hamper translation.

Using human tissue and cells in combination with organ-on-a-chip technology, we will be better able to understand the human pathophysiological mechanism underlying the progression from NAFL to NASH and subsequently to fibrosis/cirrhosis, liver cancer, and the associated cardiovascular disease. This NAFL/NASH-chip can be used to develop drugs to treat NAFL/NASH and associated diseases.