Month: January 2025

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

There are more than 500 million people worldwide who are affected by osteoarthritis (OA) and 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, such as phenotypes driven by cartilage, metabolic syndrome, subchondral bone, inflammation, and trauma injury. However, 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

In this paper from our cardiovascular research team the aim was to investigate type III collagen (COL III) turnover with the help of pharmacodynamic biomarkers in participants from the CANVAS Program.

The biomarkers of COL III formation (PRO-C3/nordicPRO-C3™) and COL III degradation fragments (C3M/nordicC3M™ and CTX-III/nordicCTX-III™) were assessed in baseline and year 3 plasma from patients enrolled in CANVAS, investigating the effect of canagliflozin in participants with type 2 diabetes. The clinical outcomes explored in this study were hospitalization for heart failure, cardiovascular death and all-cause mortality.

The study showed that higher levels of nordicPRO-C3™ and C3M at baseline were associated with a greater incidence of all investigated outcomes, whereas levels of nordicCTX-III™ at baseline were not associated with any of the investigated outcomes.

After treatment with canagliflozin, the levels of nordicPRO-C3™ decreased and levels of CTX-III increased. An increase from baseline to year 3 in nordicPRO-C3™ in the placebo arm was associated with an increased incidence of cardiovascular outcomes, and in all participants was associated with an increased risk of all-cause mortality.

Reflecting a shift in the dynamics of COL3 turnover after the treatment with canagliflozin, nordicPRO-C3™ and nordicCTX-III™ are promising pharmacodynamic tools. In future interventional trials, they can be used to monitor the impact of the canagliflozin treatment and possibly other sodium-glucose co-transporter-2 inhibitors on tissue remodeling.

Article: Association of type III collagen turnover with cardiovascular outcomes and impact with canagliflozin in the CANVAS Program: A post hoc analysis

Glioblastoma (GBM) remains a devastating disease with limited treatment options and a lack of reliable, non-invasive biomarkers to guide therapy and predict outcomes.

In this study, we identify serum biomarkers (Tau-A and C4G) that are significantly elevated in patients with recurrent GBM and that show a strong association with improved overall survival (OS) when treated with nivolumab and bevacizumab. Unlike conventional imaging or invasive methods, these serum biomarkers provide a non-invasive, dynamic, and easily accessible approach to track disease progression and response to treatment.

Tau-A and C4G offer a potential tool to stratify patients, monitor treatment efficacy, and predict survival outcomes in GBM, addressing a critical gap in current clinical practice.

We therefore encourage clinicians and researchers to explore the validation and integration of Tau-A and C4G into clinical trials and routine practice to unlock new possibilities in personalized GBM management.

Article: Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis of the skin. Patients with PsA may experience flares, which are characterized by worsening of disease activity and intensity presenting with swollen and tender joints.

The implementation of biomarkers related to PsA activity and flares, helps identifying the right patients, which will improve patient management and decrease flares. In this study, we evaluated blood-based biomarkers of inflammation, fibrosis, and joint destruction in patients with and without flares, and found that the inflammatory biomarkers VICM, CPa9-HNE, and CRPM, together with the fibrosis biomarker nordicPRO-C3™, showed a good discriminatory performance separating the PsA patients with flares from the patients without.

Such biomarkers may therefore serve as tools for quantitatively monitoring flares in PsA patients and have valuable applications in the detection of disease, as well as the monitoring of health status. This may include diagnosing, staging, predicting progression of the disease, and response to therapy.

This work was performed together with Dr. Vinod Chandran and Dr. Katerina Oikonomopoulou at the Schroeder Arthritis Institute, Krembil Brain Institute in Toronto.

Article: Investigating protease-mediated peptides of inflammation and tissue remodeling as biomarkers associated with flares in psoriatic arthritis