A drug development route for success is key but often challenging and full of uncertainties. Strategies that can increase the likelihood of success are vital. The FDA and EMA recognize that biomarker-based drug development strategies could be the solution in combination with translation research. This approach offers a biology-focused pathway that reduces time and cost and enhances the overall likelihood of success.
Our major cornerstone is combining translational models with clinically validated biomarkers to enhance drug development. For this purpose, we have assessed the ability of our biomarkers to bridge the gap between patients with gastrointestinal disease and our various model systems. Our investigations have revealed that ProteinFingerPrint™ biomarkers, such as the nordicPRO-C3™ (PRO-C3) and nordicC3M (C3M), reflecting tissue formation and destruction, can be modulated by anti-inflammatory treatments. We have assessed the biomarkers in the supernatants from our in-vitro models, the blood from in-vivo models, and the blood of patients with IBD (Figure 1.)
Figure 1. Nordic Bioscience's IBD biomarkers reflect tissue fibrogenesis and mucosal damage
These findings underline the use of the Nordic ProteinFingerPrint TechnologyTM pharmacodynamically and translationally. Browse our biomarker portfolio of pulmonary biomarkers to guide your translational research!
Various in vivo models mimicking IBD, such as the acute and chronic dextran-sodium sulphate (DSS) model, represent important translational tools to study intestinal inflammation and fibrosis in vivo. By collecting blood from these animals, intestinal tissue remodeling can be evaluated using the Nordic ProteinFingerPrint™ biomarkers to assess drug efficacy and pharmacodynamic effects in preparation for clinical trials.
In two studies using the acute (Figure 2A) and chronic (Figure 2B) DSS rodent model for the induction of colitis, the biomarkers C3M, nordicPRO-C3™ (PRO-C3), and PRO-C16 were evaluated. In the acute model, DSS induced significant mucosal damage quantified using C3M and PRO-C3. The induction of chronic intestinal damage, an elevation of type XVI collagen and fibrogenesis was observed using the PRO-C16 biomarker.
Figure 2. Nordic Bioscience biomarker levels in acute and chronic DSS-induced colitis models
| The prolonged Scar-in-a-Jar is a novel model that employs macro-molecular crowding to promote extracellular matrix formation, maturation, and deposition in vitro (Figure 3). The extracellular matrix plays a crucial role in providing structural support to cells and regulating tissue repair and regeneration by acting as a reservoir for growth factors and cytokines. Understanding the extracellular matrix dynamics is vital for developing therapeutic strategies. Using macromolecular crowding, the model becomes more 3D-like and increases complexity, making it a suitable translational model. |
By stimulating intestinal fibroblasts with pro-fibrogenic cytokines, we can model intestinal fibrosis in vitro and evaluate the efficacy of direct anti-fibrotic treatment using the Nordic ProteinFingerPrint™ biomarkers. Thus, we can determine efficacy by measuring collagen formation in the supernatants, allowing direct translation to clinical settings.
For example, by the addition of TGF-β, IL-6, and soluble IL-6R we can mimic the pathological pathways of systemic sclerosis (Figure 4A), demonstrating differences in the fibrotic burden by quantifying type VI collagen formation (nordicPRO-C6™). Moreover, the anti-fibrotic effects of compounds, such as the JAK-STAT inhibitor Tofactinib (Figure 4B+C), can be evaluated. Here, we demonstrated the anti-fibrotic effects of Tofacitinib inhibiting type III and VI collagen formation, showcasing the biomarkers applicability as efficacy biomarkers in the in-vitro setting.
Figure 4. Nordic Bioscience's biomarkers demonstrate fibrotic burden and anti-fibrotic effects of compounds
Figure 5. Scar-in-a-Jar (SiaJ) demonstrates fibrogenesis driven by activated macrophages, measured by PRO-C3
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