Non-traditional disease modeling aids the hunt for drugs to counter a growing epidemic of liver disease
In recent years, drug developers have made remarkable progress in the treatment of hepatitis C, but therapeutic solutions for an epidemic of liver disease tied to the epidemic remain elusive. The condition, known as nonalcoholic fatty liver disease (NAFLD), afflicts an estimated 30-40% of adults in the US, according to the National Institute of Diabetes and Digestive and Kidney Disease. Studies suggest 2-3% of Americans have a more progressive form of the disease, known as nonalcoholic steatohepatitis (NASH), that can lead to cirrhosis and liver cancer and is a leading cause of liver transplants. The prevalence of NAFLD has also risen rapidly among children and adolescents. There are no approved therapies for NAFLD or NASH.
The disease got its name because the liver swells with fat and the liver damage looks almost identical to what is seen in heavy drinkers. But in NAFLD, the culprits appear to be poor diet and excess weight. Outside of oncology, NASH is one of the most competitive areas in drug development today, with dozens of candidates in the pipeline including two drugs now in Phase III trials. But the complexity of the disease makes this condition incredibly difficult to model in animals. HemoShear Therapeutics, a biotech company headquartered in Charlottesville, Virginia, has found a way around this impediment. HemoShear has developed a number of different in vitro models, including one that combines primary human liver cells with other cell types found in the liver. Ryan Feaver, who heads up HemoShear Therapeutics’ NASH program, presented a talk at the World Congress on Animal Models meeting, where he described this 3D system that incorporates blood flow and key mediators in the microenvironment of these cells. (The findings were published in The Journal of Clinical Investigation Insight). He also joined a video discussion with Joe Cornicelli, PhD, FAHA, Director of In Vivo CV and Metabolic Diseases at Charles River's Integrated Drug Discovery unit and one of the scientific moderators of the meeting.