The Scramble to Find a Model for NASH Before it Becomes an Epidemic

There are currently no FDA-approved medicines for the treatment of non-alcoholic steatohepatitis, but researchers hope a new mouse model will speed the drug discovery process.

Non-alcoholic steatohepatitis, also known as NASH, is a severe form of non-alcoholic fatty liver disease (NAFLD) that is characterized by a combination of inflammation and fat accumulation in the liver. Most people with NASH are between the age of 40 and 60 and women are more likely to get the disease than men.

Severe forms of the disease can result in fibrosis, cirrhosis, liver failure or liver cancer. In fact, NASH is one of the leading causes of cirrhosis in US adults, according to the American Liver Foundation.

The exact cause of NASH is still unknown, although researchers do know that certain health conditions caused by a high-calorie diet and/or a sedentary lifestyle—including obesity, diabetes, high cholesterol and some forms of metabolic disease—put people at a higher risk of developing the disease. Unlike other fatty liver diseases caused by alcohol abuse or medication side effects, NASH occurs in people who don’t abuse alcohol.

NASH is considered a silent disease—which means that people with the disease may live with it for several years with few or no symptoms, making it difficult to diagnose. Nine out of ten patients are diagnosed with NASH by chance, Eric Hughes, Global Development Unit head at Novartis for Immunology, Hepatology & Dermatology, told pharmaphorum.com.

The disease affects three to 12 percent of the global population, according to current estimates from the National Institutes of Health. Because of rising obesity rates worldwide, current estimates suggest that the number of people with NASH will increase 63 percent by the year 2030.

Yet, awareness of the disease remains low. Only six percent of at-risk Americans had ever heard of NASH in a recent survey, Continuum Clinical reported at the third annual NASH Summit in Boston.

“NAFLD and NASH are a pending epidemicin the Western world. Figures estimate that the disease affects 80-100 million people in the United States and it is poised to overtake hepatitis C as the leading cause of liver transplants in this country,” Dr. Megan MacBride, the Director of Commercial Models at Taconic, told Laboratory Equipment. “The market is really focused on this because there are currently no approved treatments. Early stages of the disease can be reversed through diet and exercise, but there is no pill to treat liver fibrosis.”

Preclinical research is always the first stage in the development of a new drug. However, there are few NASH models currently available, leaving researchers to develop new animal models themselves or turn to a contract research organization who may have a model up and running.

“Our customers are investing a lot of resources towards research developing therapeutics for NASH. So our goal is to support that research and find ways to help researchers get to their goal faster,” MacBride said. “We are making one of our models available for this kind of research. This mouse model develops NASH symptoms when fed a high-fat, high-fructose diet with added cholesterol and palm oil. We are currently working with collaborators to verify the validity of this model.”

The ultimate goal, MacBride says, is to have models available at different stages of NASH for researchers to use in the quest to develop a therapeutic for non-alcoholic steatohepatitis.

Photo credit: Taconic Biosciences