Non-Alcoholic Steatohepatitis (NASH) is a serious and complicated disease with strong associations to other metabolic condition such as diabetes and obesity.
NASH begins with asymptomatic steatosis and can progress with subsequent liver inflammation and fibrosis leading to cirrhosis, liver failure, liver transplant and even hepatocellular carcinoma (HCC). Although there is an alarming percentage of the adult world population with at least early stages of NASH, there has not yet been a NASH drug approved for this complex disease, except the PPARα/γ agonist saroglitazar from Zydus.
The preclinical animal and cell culture models used to date have not accurately predicted drug efficacy effects once they reach the clinic, particularly with the fibrosis-associated endpoints.
In this webinar, InSphero Director of Business Development Dr. Sue Grepper focused on a novel human 3D NASH model, consisting of 4 different liver cell types relevant to this disease development. New findings were shared relating to compound modalities other than classic small molecules, as well as new quantitative fibrotic measurements achievable with this model.
PharmaNest CEO Dr. Mathieu Petitjean presented the FibroNestâ„¢ Digital Pathology AI platform for innovative phenotypic quantification of fibrosis based on histology liver slices of 3D NASH model using over 400 parameters relating to the fibrosis content, morphometry and architectural histological phenotypes. The fibrosis quantification in the 3D NASH model is extremely useful for better understanding the mechanism of action of anti-fibrotic compounds on collagen deposition.
The use of the FibroNest AI platforms allows to discover translational insights through similar quantifications and validations as performed for rodents and humans. This complex disease model and histological assay could be used as a translational drug discovery tool for prediction of efficacy and potency of anti-fibrotic compounds of in the clinic.
In this webinar, we covered:
• Modeling of key NASH hallmarks: steatosis, inflammation and fibrosis
• Scalable endpoints, including clinical biomarkers for drug efficacy testing
• Live demonstration of FibroNest™ Digital Pathology AI platform for phenotypic quantification of fibrosis based on histology tissue slices
• Efficacy testing of various modalities NASH compounds such as antibodies and small molecules