Evaluate Anti-Fibrotic Compounds in Animal Models of NASH
It is estimated that ~25% of the world’s population is affected by non-alcoholic fatty liver disease (NAFLD). NAFLD is considered to be relatively benign, but can progress to non-alcoholic steatohepatitis (NASH) in a significant number of individuals. Currently, the only therapy to treat NAFLD/NASH are lifestyle modifications (diet and exercise), and the pharmaceutical and biotech industries are actively pursuing the discovery and development of candidate therapies to address this unmet medical need.
NASH is characterized by lobular inflammation, hepatocyte ballooning and degeneration progressing to liver fibrosis. Left unchecked, NASH can progress to full blown cirrhosis and, in some instances, hepatocellular carcinoma. However, development of NASH is not universal among those affected by NAFLD, and this is one of the factors that makes modeling NASH in animal models complex. Several animal models have been identified that faithfully replicate various aspects of the disease in a reproducible manner. NASH drug discovery scientists at Charles River have have qualified two diet-induced mouse models that are useful to assess candidate agents:
- Feeding a choline deficient, defined amino acid (CDAA) diet to C57BL/6 mice
- Feeding a high fructose, high fat, cholesterol (HFHC) diet to ob/ob mice
In each case, the animals develop a characteristic change in liver histopathology consistent with NASH.
Choline Deficient, Defined Amino Acid (CDAA) Mice
- Study Paradigm
High Fructose, High Fat, Cholesterol Diet in ob/ob Mice
- Study Paradigm