US non-profit research organisation the Hamner Institutes for Health Sciences has formed a partnership with Entelos, a life sciences company focused on predictive biosimulation, to create a computer model of liver function in virtual patients.

The aim is to improve understanding of how pharmaceuticals and chemical agents sometimes damage the liver. Drug-induced liver injury (DILI) is the most frequent cause of acute liver failure and is a major factor in drugs failing to gain regulatory approval or dropping out of development, the new partners noted.

The joint programme will involve combining Entelos’ PhysioLab biosimulation platform technology with the Hamner Institutes’ expertise in liver injury and systems biology. The project will draw on “a steady stream of new knowledge coming from many avenues, including the study of patients who have experienced DILI”, the partners added.

There will be further input from Hamner research programmes employing novel liver-derived cell models and special metabolism studies, made possible by a new Hamner metabolomics laboratory.

The PhysioLab platform will incorporate this information into “a dynamic, mathematical model of liver function in virtual human patients that will account for the effects of genetic variations and other factors, such as patient sex, age, behavioural characteristics and environmental influences”, the partners explained.

In parallel, virtual rodents will be developed to improve the evaluation of pre-clinical drug effects and mechanisms of liver injury across species. This mathematical model is expected to advance understanding of drug toxicity mechanisms, identify why patients vary widely in severity of, and susceptibility to, liver injury, and help translate results from pre-clinical animal models to humans.

The wider goal of the partnership is to use the computer platform to inform the development of predictive clinical biomarkers and pre-clinical assays that will help identify patient types at increased risk of developing liver injury when exposed to specific drugs and/or drug combinations. “The platform will have many potential uses, including guiding the development of new diagnostic tests and new ways to test drug safety in the laboratory”, Entelos and the Hamner Institutes predicted.

In addition, the partnership supports the US Food and Drug Administration’s Critical Path Initiative to accelerate the development and approval of safe and effective medicines, they pointed out. As such, two FDA scientists will join the scientific advisory board for the project.