NASH-BioDuro-Sundia

NASH

BioDuro-Sundia’s pharmacology team has developed highly clinically translatable animal NASH models to evaluate drug candidates. With short NASH induction periods of 12 – 16 weeks in mice and 8 – 12 weeks in hamsters, our NASH models successfully mimic the pathogenesis of clinical NASH patients and exhibit hallmarks of NASH, including steatosis, lobular inflammation, ballooning and fibrosis.

Clinical Relevance

Obesogenic NASH models featuring all the major indicators of NAFLD to moderate NASH, including dyslipidemia, inflammation, ballooning and robust fibrosis

Pharmacologic responses

Reference compounds (OCA, Elafibrinor, Semaglutide) in our high fat diet + modified high fat diet (HFD+mHFD) NASH mouse model match the responses of these experimental drugs in clinical trials

Histology and biomarkers

Demonstrate clinically relevant levels of disease phenotype & scores

Includes steatosis, ballooning, inflammation, mallory body and fibrosis

Metabolic profiles

Similarly altered obesity markers as does human NASH, including insulin, glucose, cholesterol, triglycerides and free fatty acid

Mechanisms of action

Drugs targeting diverse biological pathways and processes

Speed

High fat diet + modified high fat diet (HFD + mHFD) mouse model with shorter induction period between 12 – 16 weeks

High fat, high cholesterol + Fructose (HFC+F) hamster models with induction period between 8 – 12 weeks

Comprehensive

5 different NASH disease models

Multiple induction methods

Obesogenic (HFD, mHFD, AMLN)

Chemical induction (CCl4, AMLN+CCl4)

Nutrient deficient (0.1MCD)

Collaborative & Responsive

Group leaders & study directors provide rapid feedbacks and consultations to your preclinical model studies, including model selection, study design and data interpretation

NASH Models

NAFLD/NASH Models & in Vitro Assays

Nutrient-deficient NASH Models

SD rat or C57bl mice fed on MCD diet for 2-3 weeks

SD rat or C57bl mice fed on 0.1MCD diet for 2-6 weeks

Chemically induced NASH Models

AMLN/HFD + CCl4 in C57bl mice, 12+4 weeks

STZ induced STAM NASH mode, 6+8 weeks

Obesogenic dietary NASH Models

HFD + modified HFD/WD in C57bl mice, 12-16 weeks

Genetic NASH Models

ob/ob mice with AMLN diet, 8-12 weeks

Hamster NASH Model

Golden Syrian hamsters

High fat & high cholesterol (HFC) plus fructose, 8-12 weeks

Fatty Liver

Liver/Renal Services

Liver weight

Liver Function: ALT, AST

Lipid panel (liver & serum): TC, TG, FFA

Insulin resistance: Insulin, BG

Histology: HE

Hepatic Fibrosis markers

Collagen type 1a, 3a, α-1 Procollage

SMA-a, TGF-b

Hydroxyproline

Histology Sirius Red staining

Hepatic Inflammation markers

TNF-a levels

Mononuclear cell infiltration

Oxidative Stress

Reactive oxygen species

Hydroxynonenal (HNE) level