Pulmonary fibrosis is a condition characterised by progressive lung scarring, resulting in a median survival of 3–5 years after diagnosis. However, the rate of lung function decline varies widely among patients with different aetiologies, posing substantial challenges in clinical management. Currently, no cure exists for pulmonary fibrosis, and pirfenidone and nintedanib, approved for idiopathic pulmonary fibrosis treatment, have partial effects in slowing disease progression and variable tolerability.
This study aimed to classify patients with pulmonary fibrosis according to blood biomarkers to differentiate distinct disease patterns, known as endotypes.
Our findings showed that blood biomarker clustering in pulmonary fibrosis identified three distinct blood biomarker signatures associated with lung function and prognosis, suggesting unique pulmonary fibrosis biomarker patterns. These findings support the presence of pulmonary fibrosis endotypes with the potential to guide targeted therapy development.
Article: Cluster analysis of blood biomarkers to identify molecular patterns in pulmonary fibrosis: assessment of a multicentre, prospective, observational cohort with independent validation
Tuesday the 4th of February is World Cancer Day. At Nordic Bioscience, we are dedicated to developing biomarker solutions that provide valuable insights on cancer, enabling drug developers to improve cancer treatment options.
In honor of this day, we would like to share a paper by our ontology team :
With increased stiffness and remodeling often driving tumor growth and metastasis, the extracellular matrix (ECM) plays a crucial role in cancer progression.
Produced by cancer-associated fibroblasts (CAFs), type XII collagen is a key regulator of ECM organization, stabilizing type I collagen fibrils, contributing to ECM stiffening, and facilitating a pro-invasive tumor microenvironment (TME). In our study, we developed the PRO-C12 ELISA, a non-invasive tool to monitor type XII collagen fragments in serum that is related to ECM stiffening and CAF activity, providing critical insights into tumor biology and metastasis risk.
By quantifying type XII collagen fragments in serum, clinicians and drug developers gain a powerful tool to non-invasively assess CAF-driven mechanisms. PRO-C12 is relevant for diverse cancer types and stages, paving the way for its integration into diagnostic workflows and clinical trials.
Article: Type XII collagen is elevated in serum from patients with solid tumors: a non-invasive biomarker of activated fibroblasts
Today is Rheumatoid Awareness Day, which we would like to honor by sharing one of our rheumatology teams’ publications from 2024.
Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation in multiple articular joints, causing pain, joint damage, and loss in joint function. Despite the successful development of disease-modifying therapies, the heterogeneity of RA means that a significant proportion of patients respond poorly to treatment. Utilizing personalized and predictive biomarkers can optimize treatment efficacy, safety, and cost.
This study explored the link between type VI collagen breakdown and the effectiveness of Tocilizumab (toci), a drug used to treat rheumatoid arthritis (RA). By measuring a specific fragment of degraded type VI collagen (C6M), researchers found that toci treatment reduced C6M levels compared to placebo and that patients who responded well to TCZ showed a greater reduction in C6M. Additionally, lower initial decreases in C6M were associated with a lower likelihood of a good treatment response.
These findings suggest that quantifying type VI collagen turnover could help predict which RA patients will benefit most from TCZ therapy, potentially leading to more personalized treatment approaches.
Article: Changes in type VI collagen degradation reflect clinical response to treatment in rheumatoid arthritis patients treated with tocilizumab
Primary sclerosing cholangitis (PSC) is a chronic liver disease that leads to a damage of the bile duct, inflammation and fibrosis.
As there is a need for non-invasive biomarkers that can accurately assess the disease severity and prognosis, this study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events.
Our findings in this study showed that nordicPRO-C3™ correlated with fibrosis stage, and nordicPRO-C3™ and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. Therefore, nordicPRO-C3™ and ELF may be utilized for staging and can act as prognostic markers in PSC, contributing to improving current screening and treatment of immune-mediated liver diseases.
Article: Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis
More than 500 million people worldwide affected by osteoarthritis (OA) are left without effective treatment options. Despite significantly different etiologies, clinical trial designs for evaluation of novel treatments still do not typically involve patient selection based on pheno- or endotypic traits.
This has likely contributed to the lack of approved disease-modifying OA drugs (DMOADs) and the high risk of unsuccessful intervention trials in the field.
In recent years, various factors indicating diverse patient subpopulations of OA have been described, including phenotypes driven by cartilage, metabolic syndrome, subchondral bone, inflammation, and trauma injury, but their underlying pathobiological mechanisms have not been fully elucidated nor have they been validated by differential treatment response.
In our recent publication we found that tissue turnover biomarkers can reliably identify knee OA endotypes across different OA populations, and these endotypes remain stable over time. This breakthrough takes us one step closer to developing a biomarker-based tool for prognostic enrichment in clinical trials, paving the way for more precise and effective OA treatments.
Article: Longitudinal stability of molecular endotypes of knee osteoarthritis patients
The crosslinked type III collagen biomarker, CTX-III, reflects fibrosis resolution and is related to intervention and survival in chronic liver disease
Introduction
Liver fibrosis progresses by deposing increasing amounts of crosslinked collagens in the extracellular matrix (ECM), destroying the liver parenchyma in the process. Treatments that hamper fibrosis could trigger the degradation of crosslinked fragments. A biomarker that measures the destruction of crosslinked collagen could open a window into the evolution of disease and the effectivity of therapy. We hypothesize that circulating fragments of crosslinked collagen type III (nordicCTX-III™) can be detected and measured to reflect fibrinolysis, and thus biomark fibrosis resolution.
NordicCTX-III™ is a biomarker engineered to detect enzymatically degraded crosslinked collagen type III. Its levels have been shown to increase after bariatric surgery, suggesting it is possible to measure systemic response to surgical intervention. Additionally, the nordicCTX-III™: nordicPRO-C3™ ratio detects a subpopulation of cirrhotic patients who respond to TIPS with significantly longer survival.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Watch “Translational Science in Pulmonary Fibrosis: From patients to cells and back—increasing success in drug development,” to learn more about what drives pulmonary fibrosis, with insights from machine learning and translational biomarkers.
Leveraging machine learning for patient stratification and advanced analytics – a COPD case study | Line Egerod
Investigating fibrosis mechanisms – what drives fibrosis in the lungs? | Dr. Naftali Kaminski
Utilizing translational biomarkers for drug development in fibrotic lung diseases | Dr. Federica Genovese
Roundtable discussion and Q&A
Scientific topics and speakers
The session will begin with an investigation into the mechanisms driving lung fibrosis, examining key processes that underlie this progressive condition. We will then delve into the role of machine learning in pulmonary research, highlighting its application for patient stratification and advanced analytics through a COPD case study.
Finally, discussions will focus on the use of translational biomarkers in drug development, offering insights into more targeted and effective therapies. This webinar is designed for researchers, clinicians, and industry professionals interested in the latest translational strategies for tackling pulmonary fibrosis.
Dr. Naftali Kaminski
Dr. Naftali Kaminski is the Boehringer-Ingelheim Endowed Professor of Internal Medicine and Chief of Pulmonary, Critical Care, and Sleep Medicine at Yale School of Medicine since 2013, with prior leadership at the University of Pittsburgh.
He is a global leader in genomic research for chronic lung diseases, including Idiopathic Pulmonary Fibrosis (IPF), COPD, severe asthma, and sarcoidosis, pioneering transcript profiling and omics integration for precision medicine.
Dr. Kaminski’s research has identified novel therapeutic targets in IPF, such as metalloproteases (MMP7, MMP19), phosphatases (SHP2, MKP5), and antifibrotic roles for thyroid hormone signaling. His team’s discoveries include the role of microRNAs (e.g., let-7, mir-29, mir-33) in lung fibrosis and the development of predictive blood-based biomarkers for IPF risk stratification and transplant prioritization.
Dr. Kaminski has authored more than 340 peer-reviewed publications in top journals, including Nature Medicine, NEJM, Science Translational Medicine, and Lancet Respiratory Medicine, while consistently securing NIH funding since 2000.
Recognized for his contributions to pulmonary research, he received awards such as the Marvin I. Schwarz Award (2010), the ERS Gold Medal for ILD (2016), and the ATS Amberson Lecture Award (2022), among many others. He is a Fellow of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) and has served in leadership roles within ATS, including as Chair of the Assembly on Respiratory Cell and Molecular Biology.
Dr. Kaminski is passionate about training the next generation of physician-scientists in genomics, bioinformatics, and systems biology, mentoring numerous successful MDs and PhDs in launching independent, well-funded careers. He continues to influence clinical and translational lung disease research as an associate editor for Thorax, BMJ, and through leadership in pulmonary genomic medicine.
Dr. Federica Genovese
Dr. Federica Genovese is the Director of Cardiovascular and Renal (CVR) Research at Nordic Bioscience. She also heads the Translational Research group.
She joined Nordic Bioscience in 2011 and assumed the role of Group leader of Kidney research in 2015 and then became Director of CVR in 2019.
Dr. Genovese focuses on developing serologically assessed markers to evaluate extracellular matrix remodeling in patients with cardiovascular and renal diseases, aiding in prognostic and pharmacodynamic evaluation.
Her team has produced the bulk of data on endotrophin, measured by the PRO-C6 assay, a fibroblast activity marker and a pro-fibrotic molecule, utilized as risk marker of adverse outcomes in multiple fibro-inflammatory diseases.
Dr. Genovese has authored more than 100 peer-reviewed publications, demonstrating her extensive contributions to the field.
Her H-index is 28, her I10-index is 42, and her research has garnered over 3400 citations as of November 2024.
Line Egerod
Line Egerod is a PhD student in the Hepatic and Pulmonary Research Team at Nordic Bioscience based in Copenhagen.
Before joining Nordic Bioscience in 2022, she worked as a machine learning engineer in Oxford, UK, and Silicon Valley, CA, US, gaining experience across various disease areas.
She is the main data steward for the ECLIPSE cohort, one of the largest and most comprehensive COPD studies to date.
Her research focuses on using interpretable machine learning models alongside inflammation and extracellular matrix biomarkers to uncover opportunities for patient stratification and personalized profiling in COPD.
Working closely with pharmaceutical companies worldwide, she and her colleagues have supported clinical research that has contributed to multiple clinical studies and publications in high-ranking scientific journals.
Tocilizumab demonstrates superior inhibition of MMP-mediated basement membrane collagen degradation compared to methotrexate or placebo
Introduction
Rheumatoid arthritis (RA) pathogenesis involves a range of immune cells, for instance T-cells, neutrophils and macrophages. They produce proinflammatory factors, such as proteolytic enzymes, which interact with tissue components such as collagens, leading to a release of unique tissue fragments into the circulation. Type IV collagen is a basement membrane supporting endothelium and epithelium. From previous studies, we know that T-cell activity may be quantified by measuring C4G, a metabolite of Granzyme B (a cytotoxic granule enzyme) mediated degradation of type IV collagen, while C4M is a marker of MMP activity. Quantifying these unique metabolites reflecting the interaction between immune cell and type IV collagen may provide a deeper understanding of the tissues affected by RA and be more relevant to disease activity and progression than simply quantifying the immune cell number or cytokines.
The aim of this study was to investigate the association between the unique immune cell activity metabolites C4G and C4M, and clinical outcomes in RA before and after intervention with tocilizumab, methotrexate (MTX) and placebo.
Type IV collagen is a basement membrane protein important for tissue integrity. It is degraded during RA leading to a destabilized tissue. The two biomarkers studied, C4G and C4M, were differentially associated with clinical outcome measures. Importantly, only C4M, a marker of MMP-derived tissue destruction, could be inhibited by tocilizumab. None of the markers were modulated by MTX.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Understanding Parkinson’s Disease Progression Through Protein Biomarkers
Parkinson’s Disease (PD) is a complex neurodegenerative disorder, primarily affecting the brain’s control over movement, thought, memory, and emotion. Early symptoms often manifest as tremors due to impaired motor skills. Underlying these visible symptoms is a cascade of molecular changes, beginning with alterations in specific proteins—one of which, α-synuclein, plays a critical role in PD pathology. In Figure 1, we have illustrated how α-Synuclein aggregates, which impairs the motor neuron.
Figure 1.Patients diagnosed with Parkinson’s Disease is affected by A) α-Synuclein aggregates affecting the motor neurons, B) Neuron loss and degeneration, and C) Blood-Brain-Barrier (BBB) leakage and neuroinflammation, by activated microglia, reactive astrocytes and extracellular matrix destruction.
In a healthy brain, α-synuclein supports neuronal communication. However, in Parkinson’s, this protein undergoes abnormal processing, driven partly by the enzyme Calpain-1, which cleaves α-synuclein into smaller, altered fragments. This early cleavage disrupts cellular function and promotes the formation of toxic aggregates, which accumulate, kill neurons, and drive disease progression. Intriguingly, these fragmented proteins can cross the blood-brain barrier and enter the bloodstream, providing a potential “window into the brain” for tracking disease activity from a simple blood sample.
At Nordic Bioscience, we have developed an innovative approach to harness this biomarker potential. Using our ProteinFingerPrint Biomarker Technology™, we can detect Calpain-1-cleaved α-synuclein fragments in blood serum with high precision. Our specific assay, α-SYN-C, captures the unique “fragment fingerprint” of PD by quantifying these cleaved fragments, which are significantly elevated in the blood of PD patients compared to healthy individuals,as illustrated in Figure 2.
Figure 2. Patients with Parkinson’s Disease has significant higher levels of α-SYN-C in serum, compared to healthy donors. The α-SYN-C biomarker detects levels of α-Synuclein cleaved by Calpain-1 in serum. The assay is technically validated for measurements in human blood samples.
This biomarker offers a non-invasive, accessible tool for monitoring Parkinson’s Disease progression and evaluating therapeutic responses. By examining α-SYN-C levels in blood samples, our technology not only provides insights into PD mechanisms but also opens doors for developing targeted therapies that address the disease’s underlying pathology. Through this work, we aim to support more accurate PD diagnostics and more effective, individualized treatments in the fight against neurodegeneration.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Fibroblast Activation Protein (FAP) generates a specific type III collagen fragment detectable in serum, which is associated with survival outcomes in patients with PDAC
Introduction
FAP expression is very low in healthy tissues, and highly upregulated in tumors Fibroblast activation protein (FAP) has unique proteolytic activity. The disease specific expression and unique proteolytic activity have made FAP an interesting protein to be utilized for drug targeting purposes. Therefore, it is important to identify the patients with FAP activity.
In this study we aimed to measure FAP activity indirectly through its proteolytic degradation of type III collagen in serum from patients with PDAC and evaluate its prognostic value.
FAP-activity can be assessed non-invasively through quantification of FAP-cleaved type III collagen and is associated with survival outcome in patients with PDAC.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
