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Nonhuman Primates: A translational model for NASH

Test your novel therapeutics for the mitigation of non-alcoholic steatohepatitis (NASH) in nonhuman primates, an ideal model for translational research.

Research Opportunity

Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in developed and developing countries1 with rates of up to 30% and often occurs as a comorbidity of obesity and other metabolic diseases. Currently, fatty liver disease and its subtype non-alcoholic steatohepatitis (NASH) lack a definitive therapeutic intervention and are managed through mitigating other comorbidities.

Most preclinical investigations of potential pharmacotherapies are done in rodent models. However, no one rodent model has proven to be highly translatable to the clinic. Their disease mechanisms differ from humans in either the induction method, morphology, or symptoms2. Many lack the defining characteristic of NASH— liver fibrosis. This absence of a highly translatable model results in a lack of understanding of NAFLD mechanisms.

Simple NAFLD is defined by a buildup of fat molecules in the liver caused by poor diet, lack of exercise and genetics. An estimated 10-20% of NAFLD patients progress to the more serious NASH3. The mechanisms driving the defining characteristics of NASH— hepatocellular damage, inflammation and liver fibrosis—are not well understood. This lack of understanding impedes the creation of potential therapeutics. Without an intervention, patients are at risk to develop cirrhosis or hepatocellular carcinoma.

Researchers at Wake Forest Baptist Medical Center have developed a novel translational nonhuman primate model, specifically African green monkeys, for NAFLD. A carbohydrate diet similar to that of many Western countries quickly produces liver inflammation in these animals4-5. Liver fibrosis naturally develops as part of their NAFLD expression. The severity of this fibrosis can be predicted by fructose exposure (see Figure 1), extent of fatty liver and age. Histologic indicators of liver disease are similar to those in humans. These translational aspects of NAFLD induction and morphology make African green monkeys the ideal model to study the disease mechanisms and potential therapeutics.

This unique model is available to industry partners to develop novel therapeutics with a higher chance of translating to the clinic, thereby reducing failure rates in Phase I trials. Our preclinical solutions include a full range of services, including principal investigators that are leading experts in this disease state, study design and management and technical services.