We will induce NASH in a genetically heterogeneous mouse population to identify the mouse model that best reproduces the human disease. We will also characterize the genetic determinants of the disease in depth at the molecular level and establish a new signature set of genes and networks that characterize NASH/NAFLD in mice, with the goal to translate these findings into targeted human therapies.
Although several compounds are being tested for the treatment of NASH, none of these has so far lead to a significant improvement of the disease. Drug development for NASH has been hampered both by the still limited understanding of the disease mechanisms and by the lack of appropriate mouse models. The success of clinical trials would greatly benefit from the development of powerful preclinical models that reproduce faithfully the pathogenesis of the human disease. Most animal models of NASH are based on different types of diet (high-fat diet, high-fructose diet, etc.), and they are often only examined on a single genetic background. While these models can reproduce some aspects of the disease, they fail to faithfully reproduce the human condition.
