NASH/MASH/MetALD PRECLINICAL CRO SERVICES
The increase in the global prevalence of NASH/MASH (Non-Alcoholic Steatohepatitis, Metabolic Dysfunction Associated SteatoHepatitis) has turned into an epidemic, urgently requiring effective therapies. Physiogenex provides high quality NASH/MASH preclinical CRO services in order to help clients develop new treatments for NASH/MASH and liver fibrosis. We provide outstanding scientific expertise, unique in vivo NASH/MASH models (see a brief overview) and golden standards in NASH/MASH biomarkers, histology analysis and blinded MASLD Activity Scoring (NAS).
As a pioneer preclinical CRO in the NASH/MASH and liver fibrosis field, we help our clients to move forward quickly with their drug candidates. We deliver original, diet-induced and benchmarked animal models of human MASLD/MASH to evaluate novel drugs efficacy. Our very fast (1 to 8 weeks) NASH/MASH models allow to rapidly demonstrate the potency of our clients’ compounds. To further confirm the drug efficacy, our diet-induced NASH/MASH models with concomitant obesity, insulin resistance, dyslipidaemia or even heart failure with preserved ejection fraction can be used (animals already on diet are available).
In each NASH/MASH model, client drugs can be compared with clinical benchmarks: elafibranor, obeticholic acid, semaglutide, firsocostat, resmetirom, etc..
NASH/MASH in vitro models
Simple hepatocytes or 3D spheroid models
Screening/efficacy tests on Hepa-RG®: 
Liver spheroids for MASH/fibrosis:
NASH/MASH in vivo disease models
Rapid (1 to 8 weeks in-life phase) animal models
Acute liver failure models:
In vivo liver lipogenesis assessment:
3-week ultra-fast NASH/MASH mouse model:
Resmetirom in the 3-week NASH/MASH mouse:
Methionine choline deficient mouse model: 
4-week CCl4 mouse model of liver fibrosis:
8-week CCl4 rat model of liver fibrosis:
Thioacetamide (TAA) rat model of liver fibrosis/cirrhosis :
Diet-induced obese, insulin resistant NASH/MASH models (15 to 30 weeks in-life phase) – animals already on diet and hamster RNAseq data available
Diet-induced obese NASH/MASH hamster model: obeticholic acid (benchmark):
Diet-induced obese NASH/MASH hamster model: assess your drug on both NASH/MASH and HFpEF
Diet-induced NASH/MASH / fibrosis obese mouse model:
Diet-induced NASH/MASH B6 (C57BL/6NTac):
MetALD in vivo models
Diet-induced hamster model – animals already on diet
Effects of incretin-based therapies and lanifibranor in hamster models of MetALD:
Effects of a pan-PPAR agonist in an obese MASH hamster model of binge drinking:
NASH/MASH preclinical CRO services
Biochemistry assays and histology
Gene expression (qPCR), plasma ALT/AST follow-up, bile acids
Cardiometabolic parameters
Biochemistry/biomarkers: liver inflammation biomarkers, liver enzymes, collagen, hyaluronic acid, plasma and liver lipids
Basic services:
- Body weight, food intake, lipid homeostasis, blood collection and tissues harvesting
- Histopathology analysis and NAFLD activity score (NAS)
Histology analysis: ORO, H&E, Sirius Red, Masson Trichrome
Immunohistochemistry: F4/80, CD68 (inflammation), cytokeratin-18, Sonic Hedgehog (ballooning), α-SMA, collagen III (fibrosis)
In vivo drug efficacy studies
In vivo lipogenesis
Complementary techniques associated with diabetes and insulin resistance: glucose homeostasis
Complementary techniques associated with lipid disorders: lipid metabolism
Our customers present their drug benefits in our models in major NASH/MASH meetings
- iLeads presents the effects of its novel FXR agonist in ALD/MetALD hamster models at APASL2024
- Hepion presents the effects of its antifibrotic drug Rencofilstat in the Physiogenex TAA rat model at the AFDD Summit
- iLeads presents a novel FXR agonist in the obese NASH hamster at AASLD Liver Meeting
- Inventiva presents lanifibranor/firsocostat combination benefits in the Physiogenex 3-week NASH mouse at ILC-EASL conference
- Inventiva presents lanifibranor benefits on both NASH and HFpEF in the Physiogenex obese NASH hamster at AASLD Liver Meeting
- CVI Pharma presents CVI-LM001 (a novel PCSK9 modulator) benefits on NASH in the Physiogenex obese NASH hamster at AASLD Liver Meeting
Our major scientific publications on NASH/MASH
- iLeadsBMS publishes a novel intestinal FXR agonist in Physiogenex obese MASH mouse and hamster models
- HepaRegeniX publishes a 1st-in-class MKK4 inhibitor to prevent liver failure in the Physiogenex CCl4 mouse model
- “Obeticholic acid raises LDL-cholesterol and reduces HDL-cholesterol in the Diet-Induced NASH (DIN) hamster model”,
Briand F, Brousseau E, Quinsat M, Burcelin R, Sulpice T. Eur J Pharmacol. 2018 - “Liraglutide improves hepatic steatosis and metabolic dysfunctions in a 3-week dietary mouse model of non-alcoholic steatohepatitis.
Duparc T, Briand F, Trenteseaux C, Mérian J, Combes G, Najib S, Sulpice T, Martinez LO, Am J Physiol Gastrointest Liver Physiol. 2019 - “A 3-week nonalcoholic steatohepatitis mouse model shows elafibranor benefits on hepatic inflammationand cell death”,
Briand F, Heymes C, Bonada L, Angles T, Charpentier J, Branchereau M, Brousseau E, Quinsat M, Fazilleau N, Burcelin R, Sulpice T. Clin Transl Sci 2020 - Briand F, Maupoint J, Brousseau E, Breyner N, Bouchet M, Costard C, Leste-Lasserre T, Petitjean M, Chen L, Chabrat A, Richard V, Burcelin R, Dubroca C, Sulpice T. Elafibranor improves diet-induced nonalcoholic steatohepatitis associated with heart failure with preserved ejection fraction in Golden Syrian hamsters. Metabolism. 2021
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