Category: Scientific Posters

Results from the Phase IIb RECITAL Trial

Posted on by Claire Hornung

Reduction of PRO-C3 and PRO-C6 fibrogenesis biomarkers in connective tissue disease-associated interstitial lung disease: results from the Phase IIb RECITAL trial

Introduction

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue disease (CTD). While cyclophosphamide is often an effective treatment for CTD-ILD, its use is limited by side effects.

In this study, Rituximab was tested as an alternative in the RECITAL phase IIb trial (NTC1862926). Both drugs improved 24- and 48-week lung function with rituximab showing fewer adverse events.

Poster

ICLAF2024 Phase IIb RECITAL Trial_Nordic BioscienceDownload

Conclusion

The decrease in nordicPRO-C6™ and nordicPRO-C3™ suggest that, besides their immunomodulatory effects, these drugs may also reduce fibrogenesis. NordicPRO-C3™ and nordicPRO-C6™, measured at baseline and as % change from baseline, are associated with an FVC response. These findings highlight nordicPRO-C3™ and nordicPRO-C6™ as promising biomarkers for CTD-ILD.

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    C1SIG Predicts All-Cause Mortality at Admission with STEMI

    Posted on by Claire Hornung

    A novel serological biomarker targeting a collagen type-I-derived matricryptin predicts all-cause mortality at admission with ST-elevated myocardial infarction

    Introduction

    ST-elevated myocardial infarction (STEMI) damages local cardiac tissue and leads to acute inflammation-driven tissue remodeling immediately after injury. A collagen type I (COL1) matricryptin cleaved by MMP-2 and MMP-9 was previously identified as being involved in left ventricular remodeling after a MI.

    We aimed to develop, technically evaluate, and quantify this COL1- derived matricryptin, named C1SIG, as a serological biomarker in a clinical cohort of STEMI patients.

    Poster

    MBE2024_C1SIG in STEMI_Nordic BioscienceDownload

    Conclusion

    C1SIG was developed as a technically robust biomarker and demonstrated as an independent predictor of
    mortality at 30 days and 1-year after STEMI, even when adjusted for multiple clinically-relevant variables.
    This COL1 biomarker could be helpful in assessing acute extracellular matrix processing in individuals after suffering a STEMI and could identify a subset of patients at increased risk of long-term outcome.

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      Evaluating CAFs Activity and Collagen Expression Profiles Using Clinically Validated Biomarkers

      Posted on by Claire Hornung

      Evaluating cancer-associated fibroblasts activity and collagen expression profiles using clinically validated biomarkers

      Introduction

      Cancer-associated fibroblasts (CAFs) are pivotal orchestrators of tumor progression through their modulation of the extracellular matrix (ECM), particularly via the deposition of collagen. Different stimuli (e.g. TGF-β, PDGF-AB, IL-1α) can activate fibroblasts and induce phenotypic alterations in CAFs, promoting a pro-tumorigenic microenvironment characterized by enhanced ECM synthesis and remodeling. Known for their heterogeneity across tumors, their collagen expression and fibrotic activity patterns remain unclear.

      In this study we aimed to elucidate differences in collagen production among various CAF subtypes from different cancer tissues, using non-invasive biomarkers to identify distinct expression profiles and fibrotic activity levels.

      Poster

      MBE2024 CAFs activity_Nordic BioscienceDownload

      Conclusion

      These findings underscore the heterogeneity in collagen production and fibrotic activity among CAFs from different indications, providing valuable insights into the ECM dynamics within distinct TMEs. Collagen-based non-invasive biomarkers demonstrate the capability to differentiate between the fibrotic activity of CAFs isolated from different tissues.

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        TGFBI Is the Local Mediator of Pathological TGF-β Activity in Pancreatic Fibroblasts

        Posted on by Claire Hornung

        Stroma-derived βigH3 (TGFBI) is the local mediator of pathological TGF-β activity in pancreatic fibroblasts and a target to treat in cancer patients with high fibrotic activity

        Introduction

        The pro-peptide of type III collagen (nordicPRO-C3™) is a circulating prognostic biomarker that can identify cancer patients with active fibrosis. Consequently, modifiers of nordicPRO-C3™ expression are potential anti-fibrotic targets for cancer. The aim was to identify genetic variants associated with circulating nordicPRO-C3™ levels and explore the relevance as pharmacological targets for treatment of fibrotic cancers.

        Poster

        ESMO2024 TGFBI_Nordic BioscienceDownload

        Conclusion

        An association between BigH3 and nordicPRO-C3™ was found by GWAS, in vitro, and in patients with PDAC: TGF-β induce BigH3, which subsequently activate fibroblasts to become fibrotic, resulting in elevated levels of nordicPRO-C3™, which in turn can be modulated by an anti-BigH3 antibody. This highlights the potential for treatment of tumor fibrosis by inhibiting BIGH3 in cancer patients with elevated nordicPRO-C3™ levels.

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          Treprostinil Reduces Fibrosis Biomarkers in the Scar-in-a-Jar Model Using a Fibrotic Cocktail

          Posted on by Claire Hornung

          Treprostinil reduces clinically relevant fibrosis biomarkers in the Scar-in-a-Jar model using a fibrotic cocktail

          Introduction

          The activation of fibroblasts and the subsequent deposition of extracellular matrix (ECM) play a pivotal role in the development of interstitial lung disease (ILD), making it crucial for novel anti-fibrotic drugs.

          In this study, we investigated the effects of a fibrotic cocktail (FC) that consists of eight pro-fibrotic and pro-inflammatory cytokines and one growth factor in the Scar-in-a-Jar fibroblast model, thereby mimicking the complex microenvironment associated with fibrotic ILDs.

          Poster

          ERS2024_Treprostinil_ScarInAJar_Nordic BioscienceDownload

          Conclusion

          The FC effectively stimulated fibrogenesis in the Scar-in-a-Jar in-vitro model, leading to elevated
          levels of the fibrosis biomarkers nordicPRO-C3™, nordicPRO-C6™ and FBN-C™. Treprostinil significantly inhibited fibrogenesis and collagen deposition quantified by ELISA. In conclusion, the Scar-in-a-Jar model is a useful tool for screening novel anti-fibrotic drugs.

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            ELP-3 as a Potential Serological Biomarker to Distinguish Fibrotic from Non-Fibrotic HP

            Posted on by Claire Hornung

            A specific elastin fragment (ELP-3) as a potential serological biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis

            Introduction

            Hypersensitivity Pneumonitis (HP) is defined by an exaggerated immune response to antigens that may develop into pulmonary fibrosis. Elastin, a structural lung protein, is susceptible to degradation by activated neutrophils during inflammation via proteinase-3. This process releases elastin fragments into circulation that can be quantified by the ELP-3 assay.

            This study aimed to evaluate serum ELP-3 in HP and compare it with healthy, IPF and chronic obstructive pulmonary disease (COPD).

            Poster

            ERS2024_ELP3_HP_Nordic BioscienceDownload

            Conclusion

            The serum ELP-3 is elevated in patients with different chronic lung diseases, particularly in HP. Notably, ELP-3 was able to separate non-fibrotic from fibrotic HP patients. These findings highlight the potential value of ELP-3 as a biomarker that provides additional clinical information beyond conventional inflammation markers.

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              CC16-HNE Is Associated with Mortality and Pulmonary Hypertension in IPF

              Posted on by Claire Hornung

              A marker of human neutrophil elastase mediated club cell secretary protein-16 degradation in (CC16-HNE) is associated with mortality and pulmonary hypertension in idiopathic pulmonary fibrosis

              Introduction

              Idiopathic pulmonary fibrosis (IPF) is characterized by epithelial injury, fibrosis, and an aberrant immune response. Club cells are essential for lung homeostasis by repairing the injured epithelium and secreting the anti-inflammatory club cell secretory protein-16 (CC16). Additionally, activated neutrophils release human neutrophil elastase (HNE) during inflammation. Our aim was to investigate if serum measurements of CC16 degradation by HNE (CC16-HNE) were related to IPF mortality and pulmonary hypertension (PH).

              Poster

              ERS2024_CC16HNE_Mortality_IPF_Nordic BioscienceDownload

              Conclusion

              Low serum CC16-HNE at baseline was associated with increased risk of mortality and a PH complication in IPF. These results indicate that a neutrophil immune response and degradation of CC16 is relevant for disease outcome. CC16 degradation by HNE could serve as a prognostic biomarker for IPF and diagnostic for a PH complication.

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                Prolonged Inflammation of Fibroblasts Promotes Formation of Type III Collagen and Fibronectin

                Posted on by Claire Hornung

                Prolonged inflammatory stimulation of fibroblasts promotes the formation of type III collagen and fibronectin in response to TGF-β1

                Introduction

                Inflammation is associated with tissue damage and the concomitant induction of wound healing responses. Pro-inflammatory cytokines such as TNF-α initiate wound healing by promoting the activation and proliferation of fibroblasts. Growth factors such as TGF-β1 drive granulation tissue formation, a type of new connective tissue formed by fibroblasts during wound healing. Fibroblast activation protein (FAP) and α-smooth muscle actin (α-SMA) identify distinct fibroblast phenotypes associated with distinct ECM remodeling.

                In this study we investigated whether prolonged inflammatory stimulation of fibroblasts would augment the fibrogenic response to TGF-β1, and the fibroblast phenotype resulting from fibro-inflammation.

                Poster

                ECM2024 TGF-β1_Nordic BioscienceDownload

                Conclusion

                TNF-α shifts TGF-β1 stimulated α-SMA+ fibroblasts towards a fibro-inflammatory FAP+ phenotype. The TGF-β1 + TNF-α stimulation is characterized by increased type III collagen and fibronectin formation, while type I and VI collagen are reduced, compared to TGF-β1 stimulation only. In conclusion, the soluble nordicPRO-C3™ and FBN-C biomarkers may be used to identify FAP + fibroblast activity, associated with fibrogenesis.

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                  Biomarkers Quantifying Changes in the Hair Follicular ECM Are Elevated in Alopecia Patients

                  Posted on by Claire Hornung

                  Biomarkers quantifying changes in the hair follicular extracellular matrix are elevated in patients with alopecia

                  Introduction

                  Alterations in the extracellular matrix (ECM) within the hair follicle microenvironment may contribute to the development and progression of non-scarring alopecia. Various ECM proteins such as type III collagen
                  and elastin are present within the hair follicle ECM. During wound healing, there is an increase in type III
                  collagen, while elastin is responsible for the elasticity of connective tissue, and its degradation might affect hair follicle function. There is also an increased immune cell infiltration, such as neutrophils, which target the hair bulb and disrupt the normal ECM architecture within the follicle leading to hair loss.


                  We aimed to investigate if biomarkers reflecting ECM remodeling could separate patients with non-scarring alopecia from healthy controls.

                  Poster

                  ECM2024 Alopecia_Nordic BioscienceDownload

                  Conclusion

                  Patients with alopecia had an increase in type III collagen formation and elastin degradation, indicating the wound healing processes as well as the loss of elasticity within the surrounding ECM of the hair follicle. Objective biomarkers quantifying changes the hair follicle and its surrounding tissues could serve as potential biomarkers of diagnosis and disease monitoring in alopecia.

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                    PRO-C22 Is Associated with Disease Severity, Activity, and Systemic Inflammation in HS

                    Posted on by Claire Hornung

                    PRO-C22 – A novel serological biomarker of tissue damage is associated with disease severity, disease activity, and systemic inflammation in patients with hidradenitis suppurativa

                    Introduction

                    Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has a substantial diagnostic delay, in part due to diagnostic challenges with lesions mimicking abscesses. Utilizing robust serological biomarkers could aid in earlier diagnosis and better monitoring of disease severity. One such potential biomarker is type XXII collagen, a fibrillar collagen located at the interface between the anagen hair follicle and the dermis in the skin.

                    In this study we aimed to evaluate a novel serological biomarker reflecting type XXII collagen turnover, in patients with HS to test its association with disease severity, disease activity, and systemic inflammation.

                    Poster

                    ECM2024 PRO-C22_in HS_Nordic BioscienceDownload

                    Conclusion

                    We developed and evaluated the novel biomarker PRO-C22 reflecting tissue damage, which was associated to disease severity, activity and correlated with systemic inflammation in patients with HS. Such biomarker may be useful in early patient stratification and efficacy of treatment marker.

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