A Deep Dive Into NASH Physiology And Drug Targets

By Jennifer Dennis-Wall, Ph.D.

In the clinical trial world, we spend a lot of time focusing on phase I-IV trials, and it’s easy to forget about the very important preclinical, basic science studies that go into drug development.

Many pharmaceuticals are developed from basic science studies, or studies that attempt to define molecular pathways in the body. When we don’t know enough about the basic science, it’s hard to pick a good drug target. One of the problems with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been a lack of understanding of the basic science. Up until the past few years, the treatment approach outside of changing lifestyle factors (i.e. diet and exercise) has been to repurpose old drugs that were used for metabolic syndrome or type 2 diabetes, since these diseases overlap in many ways. There have not been any FDA approvals for these drugs to treat NAFLD/NASH, and as a result, many of them are prescribed off label.

Pharmaceutical companies have finally caught on to the gap in research for NASH, a more severe form of NAFLD in which the liver is inflamed and begins to scar, but there are still only a handful of drugs that have made it to phase III trials.