Translational Models in Hepatic Fibrosis

Strategic drug development in hepatic fibrosis

Navigating the drug development process successfully is essential and not without challenges and uncertainties. Employing strategies that enhance the probability of success is crucial. The FDA and EMA acknowledge that biomarker-based drug development strategies, paired with translational research, could provide a viable solution. This approach offers a biology-centric approach that reduces both time and costs while improving the overall likelihood of success.

Nordic Bioscience effectively integrates innovative translational models with Nordic ProteinFingerPrint Technology™ to translate findings efficiently. By using the same biomarkers throughout various clinical development stages, they create a seamless link between preclinical models and clinical applications. This strategically chosen development pathway significantly boosts the efficiency of drug development pipelines.

Incorporating biomarker-based drug development strategies into translational research not only speeds up therapeutic advancements but also increases the chances of success. Nordic Bioscience’s advanced translational models, combined with ProteinFingerPrint™ biomarkers, play a crucial role in optimizing clinical development decision-making processes, ultimately ensuring better treatments for patients.

Publications

Translational biomarkers in hepatic research

A major cornerstone of our approach is the combination of translational models with clinically validated biomarkers to improve drug development. To this end, we have evaluated our biomarkers’ capability to bridge the gap between hepatic fibrosis patients and various model systems. These findings emphasize the pharmacodynamic and translational application of Nordic ProteinFingerPrint Technology™.

Browse our hepatic biomarker portfolio

In Vitro Model—Scar-in-a-Jar (SiaJ)

The prolonged Scar-in-a-Jar is an innovative model that utilizes macromolecular crowding to enhance the formation, maturation, and deposition of the extracellular matrix in vitro. The extracellular matrix is essential for providing structural support to cells and regulating tissue repair and regeneration by serving as a reservoir for growth factors and cytokines.

Understanding the dynamics of the extracellular matrix is crucial for developing therapeutic strategies for fibrosis. By employing macromolecular crowding, the model gains a three-dimensional like structure and increased complexity, making it a suitable translational model. This modulation demonstrates the model’s effectiveness for screening antifibrotic effects directly on hepatic stellate cells.

Figure 1. Liver Scar-in-a-Jar (SIAJ)

In Vivo Model—GAN-DIO model

The prolonged Scar-in-a-Jar is an innovative model that utilizes macromolecular crowding to enhance the formation, maturation, and deposition of the extracellular matrix in vitro. The extracellular matrix is essential for providing structural support to cells and regulating tissue repair and regeneration by serving as a reservoir for growth factors and cytokines.

Understanding the dynamics of the extracellular matrix is crucial for developing therapeutic strategies for fibrosis. By employing macromolecular crowding, the model gains a three-dimensional like structure and increased complexity, making it a suitable translational model. This modulation demonstrates the model’s effectiveness for screening antifibrotic effects directly on hepatic stellate cells.

Figure 2. Effect of Fibrotic Cocktail and ALK5 Inhibitor on PRO-C3 and PRO-C6 Levels in Hepatic Stellate Cells: A Model for Antifibrotic Screening

A MASH model: Collagen type III and Collagen type VI in Non-obese inflammation and fibrosis (NIF) mice

The rodent pro-peptide of type III collagen (rP3NP) and the Endotrophin-associated marker nordicPRO-C6™, correlated significantly with liver fibrosis progression. rP3NP, a known tissue repair and fibrosis biomarker, showed sustained elevation from 6 to 25 weeks (Left figure). Similarly, nordicPRO-C6™, associated with fibrosis, steatosis, and inflammation, was significantly elevated in NIF mice between 6 and 12 weeks, normalizing thereafter (Figure 2). As nordicPRO-C6™ is elevated in advanced fibrosis in MASH patients, these findings suggest the potential utility of rP3NP and nordicPRO-C6™ as markers for assessing anti-fibrotic therapies in NIF mice.

Figure 2. Non-fasting serum levels of rP3NP (left) and nordicPRO-C6™ biomarkers (right) in male (o) and female (•) NIF mice at different ages (n = 8–12 mice/age group). One-way ANOVA was used to compare the mean of the 3-week age group with the mean of the other age groups. Dunnetts post-tests yielded ***p < 0.001 and **p < 0.01, vs. 3-week-old NIF mice.

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