Fibroblast derived type III collagen pro-peptides (PRO-C3) in plasma are associated with outcome for patients with NSCLC treated with anti-PD1 plus chemotherapy
Introduction
Tumor fibrosis is essential for defining outcome of patients with various solid tumors including lung cancer. The cancer associated fibroblast (CAF) activation and increased deposition of type III collagen leads to immune exclusion and high interstitial pressure in the tumor microenvironment. Recently, FDA issued a Letter-of-Support to encourage use of the non-invasive tumor fibrosis biomarker nordicPRO-C3™ (type III collagen pro-peptides) in patients with solid tumors.
In thi study we investigate nordicPRO-C3™ as a prognostic biomarker in patients with non-small cell lung cancer (NSCLC) treated with anti-PD1 + chemotherapy.
Type III collagen pro-peptides (nordicPRO-C3™) is produced by activated lung CAFs and is a surrogate of fibrogenesis. High nordicPRO-C3™ levels in pre-treatment plasma associate with poor outcome for patients with NSCLC treated with anti-PD1 plus chemotherapy. These findings suggest that quantifying tumor fibrosis is important for prognostication of patients with lung cancer.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Obesity contributes to several comorbidities, including osteoarthritis (OA), which lowers quality of life due to joint pain and reduced function. Obesity worsens OA symptoms by increasing mechanical load and stress in addition to the elevated general inflammatory state. Moreover, this inflammatory drive is the prime suspect in the observed increased OA in non-weight-bearing joints of patients with obesity, such as the hands, suggesting systemic mechanisms are involved. Inflammatory mediators released by adipose tissue, including leptin, interleukin-6 (IL-6), and C-reactive protein (CRP), may contribute to heightened pain sensitivity and reduced pain thresholds in individuals with obesity.
In this study we aimed to investigate the association between the painful experience and the body mass indices of patients at baseline in a previous phase III clinical trial. Furthermore, we evaluated the change in painful experience resulting from weight loss or gain after 2 years, as measured in the last follow-up of the clinical trial.
These studies indicate that increased body weight is associated with increased OA pain which is further confirmed by reduce patient-reported obesity-related OA pain upon undergoing weight loss.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Serum immunoassays identify cartilage acidic protein (CRTAC1) as a biomarker of osteoarthritis
Introduction
Cartilage acidic protein 1 (CRTAC1), a glycosylated extracellular matrix protein, is primarily produced by chondrocytes in articular cartilage. Recent studies have indicated that circulating CRTAC1 levels are associated with the severity and progression of osteoarthritis (OA). However, CRTAC1 levels were measured using proteomic platforms, highlighting the need for easily quantifiable and reliable assays.
This study validated CRTAC1 as a promising new biomarker for OA, utilizing easily quantifiable serum immunoassays. Differences in diagnostic performance between the total and neo-epitope CRTAC1 assays were observed. In conclusion, this study offers valuable insights into the role of CRTAC1 and its degradation process in Osteoarthritis.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
April 11th marks World Parkinson’s Day, which aims to spread awareness for the millions of patients with Parkinson’s.
α-SYN-C is upregulated in patients with Parkinson’s disease
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.
Article: A fragment of Calpain-1 cleaved α-Synuclein quantified in serum is upregulated in 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.
Systemic sclerosis (SSc) affects several tissues, leading to fibrotic tissue buildup of the skin and internal organs
In our latest open-access paper in Arthritis Research & Therapy, produced in collaboration with Dr. Satoshi Kubo, we reveal 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.
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
Developing a blood-based biomarker targeting α-synuclein fragments for the early diagnosis of PD
Introduction
Parkinson’s disease (PD) affects millions worldwide and currently has no cure. Treatments focus only on managing symptoms, explaining why there is a pressing need for biomarkers and advanced diagnostic tools to enable earlier detection and better disease management. In the early stages of PD, α-synuclein—can be cleaved by Calpain I, presenting a potential target for biomarker development.
The aim of this study was to develop a sensitive immunoassay that detects α-synuclein fragments.
α-Synuclein fragments cleaved by calpain I are key early drivers of Parkinson’s disease pathology. This blood-based biomarker holds promise for enabling early diagnosis and identifying patients who are likely to respond to treatment.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
Endotrophin, quantified by a novel biomarker, is prognostic of outcome in heart failure patients
Introduction
NordicEndotrophin™ is a type VI collagen-derived matrikine associated to mortality risk in heart failure. It can be quantified by nordicPRO-C6™, which targets the C-terminal of type VI collagen α3 chain. In this study, we evaluated the prognostic performance of a novel biomarker called full-length nordicEndotrophin™, specifically designed to target the 77aa molecule at both peptide termini. We investigated the performance of the novel assay in relation to NT-proBNP and nordicPRO-C6™.
This study presents the novel biomarker of full-length nordicEndotrophin™ demonstrating comparable performance to NT-proBNP and nordicPRO-C6™ in predicting mortality risk in HF patients. The biomarker’s prognostic value remains robust even after adjusting for relevant risk factors.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
A novel urinary marker of collagen type 1 degradation reflects kidney disease severity and fibrosis in IgA nephropathy.
Introduction
In chronic kidney disease (CKD), kidney fibrosis is characterized by increased collagen deposition and turnover, especially of collagen type I (COL1), the primary protein in the kidney’s extracellular matrix (ECM). Existing techniques for assessing kidney fibrosis are highly invasive and lack sensitivity, highlighting the need for a non-invasive biomarker to identify high-risk patients before irreversible kidney function decline occurA COL1 degradation peptide (231_DDGEAGKPGP) was identified as highly associated with kidney function decline in urine peptidomics studies in CKD patients (3).
The aim of this study was to develop an immunoassay to detect this peptide in urine and evaluate its usefulness in individuals with Immunoglobulin A nephropathy (IgAN).
We developed a novel and robust urinary assay which showed potential as a non-invasive biomarker of kidney disease severity and fibrosis in IgAN. It will be of interest to evaluate its prognostic potential in appropriate kidney disease cohorts and further in other organ diseases to understand the specificity of the biomarker to CKD.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
We have highlighted some our publications that we and our collaborators worked on in the first quarter of 2024—in no particular order. We invite you to browse and read according to your interests!
Oncology
Fibroblast activation protein (FAP) is almost exclusively expressed in pathological conditions including multiple types of fibrosis and cancers, making it an optimal target for treatment.
Treatment strategies utilizing the unique proteolytic activity of FAP are emerging, thus emphasizing the importance of biomarkers to directly assess FAP activity.
CWe developed a non-invasive quantification tool for FAP-activity, specifically generated through FAP-mediated cleavage (C3F) for selection and monitoring of patients in FAP-related clinical trials.
Novel treatments for Alzheimer’s Disease are intensely sought; however, there is a dire lack of good biomarkers identifying the population with active disease progression, i.e. those in need of treatment.
We measured our Tau-A and Tau-C assays in a clinical cohort of patients with well-characterized Alzheimer’s Disease, and we observed that Tau-A was related to the CSF-levels of Aβ1-42, while Tau-C levels were indicative of fast progression, and as such identified a population of great interest.
We explored the involvement of the extracellular matrix (ECM) in various cardiomyopathies and its impact on myocardial stiffness and fibrosis. We also discussed the potential of ECM fragments for early diagnosis, prognosis, and risk stratification.
Cardiomyopathies constitute a diverse group of disorders characterized by fibrosis, ultimately leading to heart failure. Utilizing ECM biomarkers could enhance diagnosis and guide personalized therapies targeting fibrosis.
We investigated whether a degradation fragment of collagen type III (C3M) correlated with markers of inflammation and endothelial dysfunction and whether C3M was a risk marker for progression of chronic kidney disease (CKD)in persons with type 2 diabetes and microalbuminuria.
Higher serum C3M is a risk marker for CKD progression and correlates with markers of inflammation in persons with type 2 diabetes. Moreover, a doubling of serum C3M was associated with CKD progression (with mortality as competing risk) after adjustment for conventional risk factors.
In our first rheumatology publication, we investigated M6495, a new drug targeting ADAMTS-5, in healthy volunteers and osteoarthritis patients.
M6495 was safe and well-tolerated at doses up to 300mg. It significantly reduced a key biomarker of cartilage breakdown, suggesting potential to slow disease progression.
In the second study explored a new biomarker for response to Tocilizumab, a treatment for rheumatoid arthritis. Measuring type VI collagen degradation (C6M) identified patients who benefited more from the drug.
This approach has potential to personalize treatment and improve outcomes for RA patients.
In our third rheumatology publication, highlighted the need for better ways to classify osteoarthritis (OA). Current treatments only manage symptoms, and a deeper understanding of the disease is crucial.
We propose using a panel of biochemical markers to define different OA subtypes (endotypes).
We are changing people’s lives and making an impact!
“I hope this year will be as productive as last year! Congratulations to Team Nordic,” said Morten Karsdal, CEO of Nordic Bioscience, as we close out 2021 and head into 2022. “Thank you for your commitment and support to our mission: to change people’s lives through precision medicine and serological quantification of the extracellular matrix (ECM), enabled by high-precision instrumentation,” Morten Karsdal emphasized.
Nordic Bioscience has published a total of 59 publications in 2021, exclusively in peer-reviewed journals, with an average impact factor of 6.62, which shows the impact Nordic Bioscience scientists are leaving in the field. This means that quantity and quality go hand in hand, as an impact factor above 5 is a very good distinction. Even more, many of these 59 publications have an impact factor above 10 or even 20.
Nordic Bioscience’s research group is highly regarded in its field and a leader in extracellular matrix (ECM) science and quantification, proving that the company’s efforts are having an impact.
“When we visited customers in December during our normal pharma tour,” says Morten Karsdal, “I often heard how impressed our customers were with the interaction of our senior scientists and directors and the seamless coordination of the lab. “It is clear that we are all making a difference by trying to do things a little bit better every day,” the CEO added.
These successes are the culmination of a year-long team effort. The publications are based on data, and all data start with an idea for a biomarker. Assay development, assay production, assay validation, assay measurements, biobank samples, legal contracts, quality control, data reporting, and so on: all these pieces of the puzzle are required to produce publications that demonstrate value to patients and science.
Finally, the 3rd edition of Nordic Bioscience’s collagen book will be published in 2022, after the 2nd edition was downloaded 9000 times.
Get in touch
Are you interested in exploring collaboration possibilities? Enter your information in the form and a representative will contact you shortly.
