NASH PRECLINICAL CRO SERVICES

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

As a pioneer preclinical CRO in the NASH 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 NAFLD/NASH to evaluate novel drugs efficacy. Our very fast (1 to 8 weeks) NASH models allow to rapidly demonstrate the potency of our clients’ compounds. To further confirm the drug efficacy, our diet-induced NASH 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 model, client drugs can be compared with clinical benchmarks: elafibranor, obeticholic acid, semaglutide, firsocostat, resmetirom, etc..

NASH in vitro models

NASH in vivo disease models

Simple hepatocytes or 3D spheroid models

Screening/efficacy tests on Hepa-RG®:

Rapid (1 to 8 weeks in-life phase) animal models

Acute liver failure models:

In vivo liver lipogenesis assessment:

3-week ultra-fast NASH mouse model:

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 models (15 to 30 weeks in-life phase) – animals already on diet and hamster RNAseq data available

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

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

Diet-induced NASH / fibrosis obese mouse model:

Diet-induced NASH B6 (C57BL/6NTac):

NASH 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 meetings

 

Our major scientific publications on NASH

 

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