MASH and liver fibrosis

Thema:
Efficient drug development

Our flagship TNO Ldlr-/-.Leiden mouse model accurately mimics the multi-organ metabolic dysfunction and associated pathologies observed in human MASLD/MASH and fibrosis. By using translational energy-dense diets without added cholesterol, these mice develop MASH and advanced fibrosis (F3) in the context of obesity, insulin resistance, and atherogenic dyslipidemia. MASH development in Ldlr-/-.Leiden mice recapitulates underlying disease pathways observed in patients, while their human-like dyslipidemia enables simultaneous assessment of MASH, fibrosis, and atherosclerosis. This is an important advantage given the major contribution of cardiovascular disease to mortality in the MASH patient population. The model has been validated using a range of clinically relevant pharmacological interventions, including THR-β agonists, incretins (e.g., GLP-1 receptor agonists), and FGF21 analogs.

Key capabilities

Study types

Tailor-made efficacy studies for targeted pathways and mechanisms

Models

Ldlr-/-.Leiden

Output

High quality efficacy data to support informed decision-making

A powerful approach to accelerate metabolic liver disease research

TNO offers tailor-made efficacy studies with a focus on the generation of robust and relevant data. We put decades of expertise to work to design and conduct a study that is optimized for your specific research questions. An extensive range of translational readouts provides mechanistic insight into your target of interest. Our approach enables you to generate robust datasets under clinically relevant conditions and supports early go/no-go decision making in drug development.

30+

years of preclinical metabolic disease expertise

100+

completed efficacy studies across disease indications

100+

pharma, nutritional & biotech partners

60+

peer-reviewed publications

AI-powered histopathology

Our AI-based histopathology platform enables standardised, fast, and high-throughput quantification of liver pathology, including steatosis, inflammation, and fibrosis. This reduces inter- and intra-observer variability and improves sensitivity to detect treatment effects. The platform can be applied to both TNO-generated and externally generated histology samples.

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Use cases

Drug efficacy testing

Assess treatment effects on MASH progression or regression including fibrosis up to stage F3.

Mechanism of action studies

Investigate how compounds influence metabolic, inflammatory, and fibrotic processes.

Biomarker & endpoint validation

Generate translational datasets to support biomarker strategies.

A tailored path to translational insights

  • Study design

    Step 1

    We collaborate with you to define a study tailored to your compound, research questions, and selected endpoints, ensuring a clear and relevant experimental setup.

  • Model-diet selection

    Step 2

    Based on your disease area and compound characteristics, we select the most appropriate model-diet combination to maximise relevance and predictive value.

  • In-life phase

    Step 3

    The study is executed with compound administration (e.g. diet, PO, SC, IP, IV) under controlled conditions, including regular monitoring and interim data readouts.

  • Analysis

    Step 4

    We offer extensive efficacy and mechanistic readouts, combining expert pathological assessment with AI driven image analysis, alongside biochemistry, imaging, omics, and biomarker profiling.

  • Reporting

    Step 5

    Results can be summarized in a comprehensive report with expert interpretation to guide decision-making and next steps in development.

Choose the right preclinical research partner

TNO bridges the gap between preclinical MASH research and clinical outcomes. Our model-diet combinations are continuously validated against clinical data, ensuring high translational relevance.

  • Proven translatability through clinically validated models
  • Holistic understanding of MASLD disease mechanisms
  • Ethical and responsible research execution
  • Clear, actionable data to support decision-making

Ready to accelerate your MASLD-MASH research?

Get in touch to discuss your research objectives and explore how TNO can design and execute a tailored preclinical MASLD study for your compound.

In an initial discussion, we:

  • align on your research objective
  • propose suitable model-diet combinations and study design
  • provide a first outline and indicative cost range