A major hurdle in any drug discovery program is finding reliable and cost-effective assays to screen compounds prior to clinical studies. This is especially important for therapeutic areas for which animal models poorly translate into clinical results. Liver disease represents a major unmet medical need in western countries. Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting nearly one quarter of the population in the US. In 50% of patients, NAFLD can progress to non-alcoholic steatohepatatitis (NASH), an inflammatory syndrome which disrupts hepatic function. There are currently no approved treatments for NAFLD or NASH, and considerable resources are currently being expended to address these syndromes.
There exists a significant translation gap between the in vitro and animal models used to assess new molecular entities targeting liver disease and clinical results due to the complex interplay of the numerous etiologies of liver dysfunction and the difficulty in replicating the disease pathology effectively in a model for screening purposes. Utilizing primary tissue obtained directly from human donors, precision-cut liver slices (PCLS) offer unique advantages from a drug discovery standpoint.
Precision-cut liver slices are the most powerful model to screen compounds for efficacy in treating liver disease prior to a clinical trial.