NASH/MASH/MetALD PRECLINICAL CRO SERVICES

The increase in the global prevalence of MASH (Non-Alcoholic Steatohepatitis, Metabolic Dysfunction Associated SteatoHepatitis) has turned into an epidemic, urgently requiring effective therapies. Physiogenex provides high quality MASH preclinical CRO services in order to help clients develop new treatments for MASH and liver fibrosis. We provide outstanding scientific expertise, unique in vivo MASH models (see a brief overview) and golden standards in MASH biomarkers, histology analysis and blinded MASLD Activity Scoring (NAS).

As a pioneer preclinical CRO in the 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) MASH models allow to rapidly demonstrate the potency of our clients’ compounds. To further confirm the drug efficacy, our diet-induced 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 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:

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 MASH mouse model:

Resmetirom in the 3-week 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 MASH models (15 to 30 weeks in-life phase) - animals already on diet and hamster RNAseq data available

Diet-induced obese MASH hamster model: obeticholic acid (benchmark):

Diet-induced obese MASH hamster model: assess your drug on both MASH and HFpEF

Diet-induced MASH / fibrosis obese mouse model:

Diet-induced 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:

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