Pulmonary Fibrosis | Translational Biomarkers | PRO-C6

Today, Sarah explains how pulmonary fibrosis drug development can benefit from translational biomarkers, such as PRO-C6.
We need better translational tools to evaluate drugs in preclinical models and prevent drug failure in the clinic. We believe biomarkers are the necessary translational tools.
During the development of pulmonary fibrosis, there are changes in the extracellular matrix. We see destruction of the basement membrane and formation of various collagens in the interstitial matrix. We can monitor these changes in the ECM in a blood sample using protein fingerprint biomarker technology.
This study focuses on assessing the formation of collagen type VI. The type VI collagen consists of three alpha chains, but before it becomes a triple helix, the pro-peptide is cleaved and enters the bloodstream. The alpha three chain propeptide is also known as endotropic, a profibrotic hormone.
We can measure this propeptide in the bloodstream with our Protein Fingerprint technology using the biomarker PRO-C6. We investigated the potential antifibrotic effect of a drug candidate in the Scar-in-a-Jar model using lung fibroblasts stimulated with TGF-β and cultured with Ficoll to obtain this 3D-like structure. We also investigated the precision-cut lung slice model with human transplanted fibrotic tissue. Finally, the drug was also evaluated in a clinical trial in patients with idiopathic pulmonary fibrosis.
We measured PRO-C6 in the supernatant of the Scar-in-a-Jar and Precision-cut-lung-slice models and found a significant dose-dependent decrease in PRO-C6 with potential antifibrotic treatment. We were able to translate these results to the clinic, where we also observed a dose-dependent decrease in PRO-C6 in serum with the same treatment as in the Scar-in-a-Jar and Precision-cut-lung-slice models.
In conclusion, it is important to use a translational tool, in this case a blood-based biomarker, to better understand how an antifibrotic drug affects fibrosis to avoid failure in the clinic. PRO-C6 may provide a translational approach for developing new antifibrotic agents for pulmonary fibrosis. PRO-C6 is also a pharmacodynamic biomarker that can be modulated with treatment in various models and in the clinic.
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