Category: Biomarkers

α-synuclein—a critical protein in Parkinson’s disease

Posted on by Claire Hornung

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.

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    NordicPro-C3™ predictor of liver disease and alcohol-related liver disease

    Posted on by Claire Hornung

    Liver fibrosis is a progressive condition characterized by the excessive accumulation of scar tissue in the liver, often resulting from chronic liver diseases. Fibroblast activity plays a critical role in the progression of fibrosis, leading to organ function loss and liver-related complications. Liver fibrosis accounts for approximately 2 million deaths worldwide, while alcohol-related liver disease (ArLD) causes over 330,000 cirrhosis deaths globally every year.

    In two recent studies, we investigated the fibrogenesis biomarker nordicPRO-C3™ in the context of advanced liver disease and full-spectrum fibrosis in alcohol-related liver disease. Our goal was to assess the nordicPRO-C3™ biomarker’s potential prognostic value and clinical utility as a predictor of outcome, and our results are very promising.

    The nordicPRO-C3™ biomarker is capable of identifying advanced liver fibrosis and alcohol-related liver disease, providing a new clinical utility tool

    In the first paper, published in JHEP Reports, we conducted investigations using two distinct cohorts of patients with compensated cirrhosis of mixed etiologies. In both cohorts, a 2-fold increase in nordicPRO-C3™ at baseline was associated with a significant hazard increase for liver-related events. Notably, nordicPRO-C3™ exhibited prognostic significance.

    The identification of nordicPRO-C3™ as an independent prognostic factor for liver-related clinical outcomes has important implications for both drug development and clinical practice. By understanding the dynamic range of nordicPRO-C3™, researchers can improve its utility as a predictive marker in drug trials, enabling the development of targeted therapies to mitigate fibrosis progression and improve patient outcomes.

    In a clinical setting, the integration of nordicPRO-C3™ measurement alongside established markers such as fibrosis-4 index (FIB-4) or transient elastography (TE) may enhance risk stratification and inform treatment decisions. Early identification of patients at higher risk for liver-related events can facilitate timely interventions, such as disease monitoring, lifestyle modifications, and appropriate therapeutic interventions.

    In the second paper, published in Liver International, we assessed nordicPRO-C3™ models to predict liver-related events in patients with a history of excessive alcohol use but without a confirmed diagnosis of chronic liver disease. Our findings our promising for improving risk stratification and clinical outcomes in alcohol-related liver disease.

    A prospective cohort study involving patients with alcohol-related Liver Disease (ArLD), was conducted and divided into a derivation cohort of secondary care patients and a validation cohort of primary care patients. Baseline variables, including nordicPRO-C3™, were utilized to develop a prediction model known as the ALPACA score. The prognostic accuracy of the ALPACA score was compared to existing tools such as the enhanced liver fibrosis (ELF) test, FIB-4, TE, and the ADAPT score (developed for fatty liver disease).

    The ALPACA score demonstrated excellent discriminative accuracy in both the derivation and validation cohorts, comparable to TE and the ELF test, and superior to FIB-4, nordicPRO-C3™ alone, and the ADAPT score. Importantly, the ALPACA score provided reliable prognostic performance independent of the baseline fibrosis stage. This breakthrough has the potential to revolutionize risk stratification and patient management in primary and secondary care settings.

    NordicPRO-C3™ has recently become available on the Roche-COBAS high-precision platform, paving the way for its commercial availability worldwide in the near future. This accessibility will enable widespread adoption of nordicPRO-C3™-based scores, leading to improved risk prediction and better outcomes for individuals.

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      Serological biomarkers are different

      Posted on by Claire Hornung

      Biomarkers are more than just omics categories

      Biomarkers aren’t just confined to different omics categories; various classes are referring to the types of serological measurements.

      Consider cytokines, growth factors, receptors, kinases, transcription factors, intracellular proteins, extracellular proteins, and a subset within that—Extracellular Matrix (ECM) proteins. The common denominator in most pathologies is a loss of balance between different ECM proteins, especially collagens.

      Biomarkers are more than just omics categories

      This excessive destruction and deposition of proteins significantly propel the progression of end-stage diseases, culminating in organ dysfunction, failure, and, ultimately, death.

      Diverse cytokines and growth factors orchestrating via specific receptors and kinases lead to ECM destruction and deposition, making ECM the converging pathway for multiple stimuli.

      By the end of the day, what matters is to reverse ECM deterioration, or even undo, organ damage and function decline. Reversing organ damage can be achieved by stopping ECM deterioration. To truly reverse organ damage and restore organ functionality in patients, we need to repair the ECM to its normal balance.

      We at Nordic Bioscience believe that the answer lies in effecting change at the tissue level—the key to reversing organ damage and, in turn, revitalizing organ function.

      Have you considered if your treatment or pathway is affecting tissue formation or degradation? If so, feel free to browse our unique ECM biomarker portfolio.

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        The CPa9-HNE biomarker in Crohn’s and Colitis

        Posted on by Claire Hornung

        CPa9-HNE ELISA has emerged as a novel serum calprotectin biomarker

        Status quo: Crohn’s and Colitis biomarkers

        Conventional serum calprotectin biomarkers are often not as clinically useful as the fecal versions, which is related to the half-life of calprotectin in blood (only 5-6 hours), leading to dissociation of calprotectin protein. The short half-life of calprotectin in blood reduces the window in which the current serum calprotectin ELISA assay can detect calprotectin dimer protein, which is composed of monomers S100A8 and S100A9.

        By applying the Protein Fingerprint technology, we have identified a neo-epitope of the S100A9 monomer of calprotectin derived from proteolytic cleavage by human neutrophil elastase (HNE). This ELISA assay is referred to as the CPa9-HNE assay and is a new and innovative method for quantification of calprotectin in serum developed by Nordic Bioscience.

        Inflammatory Bowel Disease (IBD) flares in the intestines.

        A new tool to measure… calprotectin

        Patients with Crohn’s disease and ulcerative colitis have been found to show significantly higher levels of CPa9-HNE in their serum than healthy subjects, with the AUC reaching 0.98 (CI: 0.97-1.00, p<0.0001) for CD and 0.96 (CI: 0.92-1.00, p<0.0001) for UC, proving the assay’s efficacy in distinguishing between disease states.

        In comparison, the MRP8/14 serum calprotectin assay from Bühlmann Lab, while also used to identify IBD, showed poorer separation between patients and healthy subjects, with AUCs of 0.72 (CI: 0.59-0.86, p=0.0025) for UC and 0.70 (CI: 0.56-0.84, p=0.0046) for CD, respectively.

        The CPa9-HNE biomarker showed a better correlation with the endoscopic score for Crohn’s disease (SES-CD) and ulcerative colitis (MES) than the FCP. At the same time, the MRP8/14 assay and neutrophil count showed no significant correlation with endoscopic scores for IBD patients.

        To investigate the accuracy of the CPa9-HNE, we performed a received operator characteristic curve, demonstrating CPa9-HNE with acceptable accuracy to identify patients with IBD in remission vs. active disease.

        Finally, we demonstrated that the CPa9-HNE biomarker could detect the calprotectin neo-epitope only in the supernatant of in vitro activated primary human neutrophils, but not in inactive primary human neutrophils. This was in contrast to the MRP8/14 serum CP assay of the Bühlmann lab, as both inactive and activated primary human neutrophils secreted detectable levels of calprotectin.

        CPa9-HNE ELISA proved to be a novel serum calprotectin biomarker with significant clinical potential as a biomarker for patients with IBD to monitor disease activity and neutrophil activity.

        However, circulating calprotectin metabolites released from locally inflamed mucosa are not be dissociated further. They can be readily quantified using an ELISA-based technique called Protein Fingerprint technology. This refined ELISA technique quantifies protein metabolites or neo-epitopes derived from proteolysis that reflect local tissue inflammation and remodeling.

        Read the full article here.

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          NEJM Evidence study shows PRO-C6 to Segregate HFpEF

          Posted on by Claire Hornung

          PRO-C6 Findings In NEJM Evidence to Help Patient Segregation in HFpEF

          A persistent problem remains a challenge in HFpEF – patient heterogeneity.

          We need the right patients for the right treatment, but how do we get it to them? We believe that one approach to solving this problem is to improve patient segregation and endotyping.



          In collaboration with Bristol Myers Squibb and University of Pennsylvania, we recently identified a subset of patients at a very high risk of adverse outcomes, all characterized by increased fibroblast activity. Using our PRO-C6 biomarker assay we can accurately quantify this risk profile and differentiate patients based on how likely they are to be re-hospitalized or have all-cause mortality due to heart failure.

          These findings were recently published in NEJM Evidence.

          So how do we deal with patient heterogeneity?

          We believe it is time to give physicians and clinicians a better tool than what is available now.

          This is endotrophin endotyping, heart failure risk stratification redefined.

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            Biomarkers in Drug Development

            Posted on by Claire Hornung

            The Protein Fingerprint Technology

            Through our Protein Fingerprint technology, we identify fragments of the Extracellular Matrix (ECM) that are released from affected tissues and develop blood-based biomarker assays to quantify disease activity with the aim of precision medicine.

            By quantifying tissue remodeling, our biomarkers provide true prognostic and predictive value, as we can select the patients who are most likely to respond to a given treatment and thereby function as surrogate biomarkers for clinical trials. Our biomarker assays not only enable faster drug development but also improve disease outcomes for chronically ill patients by predicting treatment response.

            Watch more videos about Nordic Bioscience’s biomarkers and the ECM on our YouTube channel!

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              Use of Translational Biomarkers in Pulmonary Fibrosis

              Posted on by Claire Hornung

              PRO-C6 as a pharmacodynamic biomarker

              During the development of pulmonary fibrosis, there are changes in the extracellular matrix. We see the destruction of the basement membrane and the formation of various collagens in the interstitial matrix.

              We can monitor these changes in the ECM in a blood sample using Protein Fingerprint biomarker technology.

              Watch more videos about the extracellular matrix and the Protein Fingerprint on our YouTube channel!

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                Endotrophin as a Novel Biomarker in HFpEF – Identification of a High-risk Endotype

                Posted on by Claire Hornung

                Identification of a High-risk Endotype

                Heart failure with preserved ejection fraction (HFpEF) is a highly complex and heterogeneous syndrome that causes substantial morbidity and mortality, positioning this disease as one of the biggest unmet medical needs today.

                The past years have seen great scientific and clinical efforts on elucidating the driving mechanisms, but much remains unknown and successful therapies at still largely absent.

                One of the biggest challenges to treating HFpEF is the heterogeneous nature of the syndrome. Risk assessment by conventional biomarkers has not led to any significant therapies, but selection of a more homogenous patient population might be the way forward.

                Fibrosis is a hallmark feature of HFpEF pathology, acting as a driver of outcome. Understanding the intricate pathways that lead to fibrogenesis, and how they ultimately impact pathogenesis, is important for understanding how to treat HFpEF. We have developed a biomarker of fibroblast activity, PRO-C6, which independently and with high precision can identify a subset of HFpEF patients with a very elevated risk of adverse outcome.

                Watch more videos about Nordic Bioscience’s biomarkers and technology on our YouTube channel!

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