Category: 2-Minute Science

Multiple sclerosis (MS) is characterized as an inflammatory neurodegenerative disease in the central nervous system (CNS), presenting with significant inter- and intra individual heterogeneity. The pathological hallmarks of active MS lesions are blood brain barrier (BBB) disruption, inflammation, and demyelination with axonal damage. Blood-based biomarkers reflecting tissue changes in immunology and/or neurobiology may reflect MS pathology and be easily accessible.

In our latest publication in “Multiple Sclerosis and Related Disorders”, we introduce nordicCAN^TM, a technically robust assay, which targets a fragment of the α2 chain of type IV collagen to detect canstatin (CAN) in human serum. This was evaluated as a biomarker for MS together with other type IV collagen biomarkers, and the results showed TUM to be an excellent diagnostic biomarker in MS, while CAN and PROC4 were both acceptable diagnostic biomarkers.

To our knowledge, this is the first study to quantify fragments of type IV collagen in serum from patients with MS, and such biomarkers may be used to assess patients’ eligibility for targeted treatments and fill a part of the gap for biomarkers in clinical management and trials.

The Hidradenitis Suppurutiva Awareness Week is held annually to spread knowledge about the disease and how it affects patients. Affecting roughly 1% of the population, HS causes significant physical and emotional challenges that are often overlooked. The HS awareness week aims to spread knowledge about the disease and how it affects patients.

HS is believed to result from a complex mix of genetic predisposition, lifestyle factors, and immune system dysfunction, driving a continuous cycle of inflammation. It commonly presents as painful nodules, abscesses, draining tunnels beneath the skin, and scarring.

These symptoms often cause physical discomfort and disability, affecting quality of life, personal relationships, and career opportunities.
People living with HS respond differently to treatments, and we believe that raising awareness and supporting research is key to developing tailored treatment strategies that truly address their challenges.

Our dermatology biomarkers enable precision medicine by providing information about ongoing pathological processes, such as damage and repair, within the ECM. This can guide targeted treatments and therapies, enhancing patient outcomes and personalized medicine approaches. At the same time, our markers, supported by our long history of experience and expertise, expedite drug development by specifically identifying target populations and reducing costs, over proteomic providers’ hopes to hit the right target by chance.

April 11th marks World Parkinson’s Day, which aims to spread awareness for the millions of patients with Parkinson’s.

Parkinson’s is the fastest growing neurological disease and there currently is no cure. One of the main challenges in developing effective treatments for Parkinson’s disease is the need to diagnose patients early, identify those with rapid disease progression, and monitor treatment response through reliable indicators.

Nordic Bioscience has developed a blood-based biomarker targeting a pathological fragment of alpha-synuclein cleaved by Calpain-1, which aggregates into fibrils as part of the disease process. This biomarker has been shown to be upregulated in patients with Parkinson’s disease. Since this pathological fragment is generated before fibril aggregation occurs, we can identify patients early.

In our paper published in Scientific Reports, we describe the development and potential of this biomarker in two clinical cohorts of patients with Parkinson’s Disease.

It can be a cumbersome clinical challenge to monitor subtle changes in collagen turnover in Systemic Sclerosis (SSc), a complex autoimmune condition marked by skin and organ fibrosis.

We are excited to share our latest open access paper in Arthritis Research & Therapy, produced in collaboration with Dr. Satoshi Kubo. Our study reveals that although type VII collagen—an essential anchoring fibril in the skin’s basement membrane—is not directly linked to skin stiffness, its turnover is significantly elevated in SSc, even when disease activity appears low.

In this study, we have shown that the dynamics of type VII collagen remodeling can be quantified using the serological biomarker PRO-C7, measuring type VII collagen formation, and it’s counterpart measuring collagen degradation, C7M. By tracking these biomarkers, clinicians can identify patients with hidden yet active collagen turnover, allowing for more personalized treatment strategies and better monitoring of therapeutic responses.

Article: Accelerated Type VII collagen turnover in systemic sclerosis patients, reflected by serological neo-epitope fragment biomarkers

We recently published an open assess review, where we and our collaborators have investigated the novel concept of “hot” and “cold” fibrosis—published in the Journal of Hepatology.

Fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix (ECM) components, particularly collagens, leading to tissue scarring and organ dysfunction. The concept of “hot” and “cold” fibrosis has recently emerged to help understanding the immune landscape within fibrotic tissues and how ECM and immune cell interactions could be new targets for future fibrosis treatment.

This review provides a new angle of describing fibrosis as “hot” or “cold”, which refers to the immune status within fibrotic tissues and the nature of fibrogenic signaling. Whereas hot fibrosis is characterized by active immune cell infiltration and inflammation, cold fibrosis is associated with auto- and paracrine myofibroblast activation, immune cell exclusion and quiescence.

We demonstrate that pharmacodynamic biomarkers reflecting ECM remodeling are promising tools to monitor fibrotic and inflammatory processes in hepatic diseases, allowing to identify disease profiles associated either with hot or cold fibrosis. This also enables tailored strategies—such as combining anti-fibrotic drugs with immune-stimulating therapies—to optimize treatment efficacy.

Article: Hot and cold fibrosis: The role of serum biomarkers to assess immune mechanisms and ECM-cell interactions in human fibrosis

September is pulmonary fibrosis (PF) awareness month—a progressive lung disease that affects over 200,000 people in the United States alone. PF causes scarring of lung tissue, leading to severe breathing difficulties and reduced quality of life.

At Nordic Bioscience, we are dedicated to advancing the development of biomarkers that provide deeper insights into disease progression in pulmonary fibrosis. Together with our collaborators, we contributed to the Lancet publication: Cluster analysis of blood biomarkers to identify molecular patterns in pulmonary fibrosis: assessment of a multicentre, prospective, observational cohort with independent validation.

This research represents a step forward in identifying endotypes that can help improve the monitoring of the disease and guided therapy, ultimately enhancing patient care.

We hope our findings encourage continued research and collaboration, working together to make a lasting impact!

Assessing disease burden and treatment response in ulcerative colitis (UC) remains challenging, often leading to treatment withdrawal and unresolved disease activity. These challenges highlight the need for better, non-invasive biomarkers to monitor disease activity and predict treatment outcomes.

In our recently published paper “Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis”, we identified C7M (MMP-9/13-degraded type VII collagen α1-chain), nordicPRO-C3™ (type III collagen formation), and PRO-C22 (turnover of type XXII collagen) as biomarkers of endoscopic disease severity and treatment response in UC.

We found that a combination of nordicPRO-C3™ and PRO-C22 predicted endoscopic outcomes at week 24, while lower levels of C7M and the C3M/nordicPRO-C3™ ratio were associated with endoscopic response. Notably, this is the first time that MMP-mediated type VII collagen degradation has been linked to disease severity in UC, highlighting its potential role in epithelial damage and barrier dysfunction.

These biomarkers provide a non-invasive means to assess transmural disease activity and disease extent, addressing a critical gap in disease burden monitoring. Incorporating these biomarkers into clinical practice could improve UC management by refining diagnostic accuracy for predicting endoscopic response prior to treatment adjustment.

Article: Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis

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