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, in combination with translation research, could be the solution. This approach offers a biology-focused pathway that not only reduces time and cost but also enhances the overall likelihood of success.
A major cornerstone of ours is to combine translational models with clinically validated biomarkers to enhance drug development. For this purpose, we have assessed the ability of our biomarkers in bridging the gap between pulmonary fibrosis patients and various model systems. Our investigations have revealed that ProteinFingerPrint™ biomarkers, such as nordicPRO-C6™ (PRO-C6, also known as Endotrophin), show dose-dependent modulation in response to antifibrotic treatment. We assessed both in the blood of idiopathic pulmonary fibrosis (IPF) patients and in the supernatant of pulmonary fibrosis models (Figure 1) [7,8,9].
Figure 1. NordicPRO-C6™ assessed in the blood of IPF patients and supernatant of fibrosis models.
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!
Figure 2. Prolonged Scar-in-a-Jar model in vitro. | The prolonged Scar-in-a-Jar is a novel model that employs macro-molecular crowding to promote the formation, maturation, and deposition of extracellular matrix in vitro. This makes the model more 3D-like and increases the complexity making it a suitable translational model. By stimulating primary fibroblasts with pro-fibrogenic cytokines we can model lung fibrosis in vitro and evaluate direct anti-fibrotic treatment efficacy. Afterwards, the Nordic ProteinFingerPrint™ biomarkers can be measured in the supernatants to determine efficacy, subsequently allowing for direct translation to clinical settings. |
The figures show how nordicPRO-C3 (formation of type III collagen; PRO-C3) and nordicPRO-C6™ (formation of type VI collagen; PRO-C6) increase when stimulating lung fibroblasts with a fibrotic cocktail. In addition, PRO-C3 and PRO-C3 levels are affected and can be decreased when stimulating the fibroblasts and treating them with Omipalisib. This modulation shows that the model is applicable for screening of antifibrotic effects directly on the fibroblasts. |
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Figure 4. C3M levels lowered in mice after bleomycin treatment. | The bleomycin model has become an important translational model for pulmonary fibrosis. The model allows us to study pulmonary fibrosis in vivo. To assess efficacy, Nordic ProteinFingerPrint™ biomarkers are measured in the blood of patients. The graph shows how C3M (type III collagen degraded by MMP) is increased in bleomycin-treated mice compared to saline, meaning that fibrotic processes are present in the model. Also, C3M levels are lowered to the same level as saline when adding an antifibrotic treatment to the bleomycin-treated mice. The treatment effectively reduced collagen degradation and fibrosis, restoring the tissue environment. |
The SiaJ model goes 3D with the new 3DPROFIB in partnership with Ectica Technologies. This new platform offers the possibility to analyze Nordic Bioscience ECM formation biomarkers from the supernatant of fibroblasts growing in a 3D synthetic and animal-free hydrogel matrix, increasing the translational character of our model and supplementing the biomarker readout with imaging-based readouts.
This platform:
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The 3D network of primary fibroblasts responds to pro-fibrotic cytokine stimulation (ions of PDGF-BB and TGF-β). |
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