Can biopsy confirmed disease progression give quality data?
Contract research services within NASH
We have established and validated a diet-induced obese (DIO) mouse model of non-alcoholic steatohepatitis (NASH) for chronic efficacy studies. The DIO-NASH model exhibits key hallmarks of NASH, including steatosis, inflammation and fibrosis, uniquely identified by pre-study liver biopsy and objectively assessed by individual histological changes from baseline (pre) to study end (post) using the clinical-derived NAFLD activity score and fibrosis stage.
Animals are constantly being diet-induced to allow for monthly conduction of NASH studies, and our pre/-post liver biopsies have proven especially valuable to our customers.
- Diet-induced obese (DIO) mouse model of NASH (DIO-NASH)
- Obese diet-induced ob/ob mouse model of NASH (ob/ob-NASH)
- Chronic (8-12 weeks) efficacy studies in mice randomized into study groups based on individual pre-biopsy histological assessment
- Metabolic assessment (body weight, food intake, glycaemia, insulinemia and glucose tolerance)
- Histological assessment of hepatic steatosis, inflammation, ballooning degeneration and fibrosis (HE, Sirius Red, IHC) levels
- Pathologist evaluated NAFLD Activity Score (NAS) including Fibrosis Stage
- Hepatic collagen content by hydroxyproline assay
- Hepatic triglyceride and cholesterol content
- RNA sequencing and bioinformatics
Gubra DIO-NASH model
The Gubra diet-induced obesity (DIO) mouse model of NASH (DIO-NASH) is based on wild-type C57BL/6 mice offered a diet high in fat, fructose and cholesterol 26+ weeks prior to pre-biopsy collection. Only animals demonstrating hepatosteatosis and fibrosis are enrolled into study groups.
Gubra ob/ob-NASH model
The Gubra accelerated mouse model of NASH (ob/ob NASH) is based on the leptin-deficient ob/ob mouse offered a diet high in fat, fructose and cholesterol for 12 weeks prior to pre-biopsy collection. Only animals demonstrating hepatosteatosis and fibrosis are enrolled into study groups.
Gubra NASH posters and publications
Gubra benchmark characterization paper: Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis
Gubra DIO NASH model characterization paper: Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy
Gubra benchmark poster: Comparative metabolic and hepatic effects of liraglutide, elafibranor and obeticholic acid in diet-induced and genetically obese mouse models of biopsy-confirmed NASH.
Read review of preclinical models of NASH: Mouse models of nonalcoholic steatohepatitis in preclinical drug development
Global characterization of gene expression regulation by clinical candidates liraglutide, elafibranor and obeticholic acid in a diet-induced obese mouse model with biopsy-confirmed NASH.
“Gubra’s DIO NASH model services are truly best in class. The ease and speed with which we could initiate studies and receive data was incredibly helpful in advancing our program. In addition, their ability to examine liver histopathology pre-and post-treatment was key to understanding efficacy.”
Director of Biology | Metacrine
Find out more about the partner program between Boeringer Ingelheim Pharma and Gubra.
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