To support clinical study for anti-fibrosis therapeutics, Stelic Institute & Co. has developed translational research-related technologies including biomarkers and various mouse models corresponding to human fibrosis-associated diseases. The Total NASH Program is the best example of our translational research program. NASH patients are now estimated at 5.7% of the general US population and one third of NASH patients show progression to liver cirrhosis. Despite the urgent need, there is no effective treatment at present. Our NASH program will contribute to the development of anti-NASH therapeutics.
NASH biomarkers
Current parameters in the clinical development of anti-NAFLD/NASH drugs are mostly serum ALT, fat imaging and liver biopsy, but each have significant limitation. Serum ALT and fat content decrease in parallel with the progression of fibrosis, thus are not good predictors of a patient’s prognosis. Although liver biopsy remains the gold standard, the fibrosis score for NASH is largely determined by the length of the specimens [sampling heterogeneity] due to the ‘salt and pepper’ distribution of injured sites. In addition, pediatric NAFLD shows an altered histological pattern, indicating that liver biopsy does not fit the long-term progression of an individual NAFLD patient. To overcome these limitations, Stelic Institute & Co. have established both serum and imaging biomarkers that reflect NASH-based fibrotic histology. Our non-invasive biomarkers can calculate the degree of fibrosis at whole liver levels, thus bringing quantitative endpoints into clinical practice.
NASH animal model
A good animal model is useful for revealing the mechanism of NASH, thus contributing to the establishment of effective treatments. Animal models for NASH are generally divided into 2 categories: genetic leptin-mutation models and dietary methionine/choline-deficient models. However, there is little evidence to support the assertion that the previous models replicate either the phenotype or the pathogenic mechanisms of human NASH. Since NASH is a clinico-pathologic syndrome encompassing a wide range of fatty liver disease, histological similarity is the most important attribute for animal NASH models. Based on the concept that fibrosis is one of the phenotypes of tissue remodeling after insult and NASH is the hepatic manifestation of metabolic syndrome induced by mild inflammation, Stelic Institute & Co. have established novel NASH animal model showing similar histopathology to human NASH. Stelic’s proprietary NASH model has significant advantages:
- Sequential change from steatosis, NASH to fibrosis can be investigated within 2 weeks.
- NASH-based LC-derived HCC can be investigated in a short period relative to existing cancer models.
- Clear disease onset and 100% reproducibility.
Given the advantages of our NASH models, we also offer the contracting research service to support the pre-clinical study investigating the drug efficacy of customers’ compounds in treatment of metabolic disorders, NASH, HCC and so on.
