We are thrilled to unveil our latest review, delving deep into the evidence surrounding the impact of Disease-Modifying Therapies (DMTs) on the quality of life for individuals battling Multiple Sclerosis (MS).

Key findings:

• We analyzed 38 trials spanning from 1999 to 2023, involving over 23,000 participants.
• DMTs have the potential to significantly improve quality of life
• However,  there seems to be no generally accepted standard for assessing disease-specific QoL in PwMS, and rarely is this end point in the focus of DMT-evaluating trials. 

Join us in spreading awareness about the critical importance of quality of life in MS care. Together, let's advocate for better-designed trials that reflect the needs of patients.

Read full article: Clinical trial evidence of quality-of-life effects of disease-modifying therapies for multiple sclerosis: a systematic analysis

The latest publication from the RC2NB team published in Nature Reviews Neurology. Neurofilament proteins have emerged as valid biomarkers of neuronal injury and loss. Based on our previous review from 2018 that summarized what was known at the time about neurofilaments as biomarkers for neurological disorders, we here provide an update on the structure and function of neurofilaments, analytical approaches, and challenges in different clinical contexts. This review focuses on the progress made in recent years towards the clinical application of neurofilaments as a biomarker in various neurological disorders.

Read the full article here: Neurofilaments as biomarkers in neurological disorders — towards clinical application

In the newest study published in BMJ Health Care & Informatics, the Pragmatic Evidence team delved into the realm of digital biomarkers, aiming to uncover the essence of this evolving concept. All studies that prominently use the term "digital biomarker" were assessed. However, most of them did not provide a definition, and out of the 128 articles that did provide a definition, 127 used different ones. This indicates a clear lack of consensus in this emerging field. Our overview aims to guide the development of a more harmonized and widely accepted definition.

Read the full publication here: Definitions of Digital Biomarkers

Researchers from the University of Basel and the University of Toronto, Mainz have identified a potential new mechanism by which B cell therapy may protect the brain in MS patients. This study, published in Science Translational Medicine, suggests B cell depletion may safeguard brain tissue beyond its known effect of reducing acute inflammation.   

Check out this work published by the Pröbstel lab; Tradite Neziraj, Elisabeth Pößnecker and Anne-Katrin Pröbstel.

Congratulations to all the contributors for this excellent work!

Read full article here: https://www.science.org/doi/10.1126/scitranslmed.adi0295 

A significant advancement in the field of multiple sclerosis (MS) treatment! The research led by Patrick Vermersch, Cristina Granziera and Gavin Giovannoni surrounding the CD40–CD40L costimulatory pathway has paved the way for a potential game-changer - Frexalimab, a second-generation anti-CD40L monoclonal antibody.

The CD40–CD40L pathway plays a crucial role in regulating both adaptive and innate immune responses and has long been implicated in the pathogenesis of multiple sclerosis. With its intricate involvement in the disease process, targeting this pathway has become a promising avenue for developing effective treatments. Frexalimab represents a new frontier in MS therapeutics. As a second-generation anti-CD40L monoclonal antibody, it holds the potential to provide novel and improved solutions for individuals affected by this complex neurological disorder.

Multiple sclerosis manifests in two principal forms: relapsing and progressive. Relapsing MS is characterized by recurrent attacks, initially with remissions, but can lead to lasting disability over time. On the other hand, progressive MS involves continuous worsening. Understanding these distinct forms has been essential in tailoring effective treatment approaches. Relapsing multiple sclerosis primarily involves the adaptive immune system, orchestrated by circulating B lymphocytes that traffic into the central nervous system. In contrast, progression is mediated by both the adaptive and innate immune systems. The editorial accompanying this research by Stephen L. Hauser emphasizes the significance of addressing these different mechanisms in the treatment of  two forms of MS. https://www.nejm.org/doi/full/10.1056/NEJMe2314434

The future of MS treatment is on the horizon, and we are eager to witness the positive changes that may result from this innovative research.

Read the full original article here: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2309439?articleTools=true

Exciting news about the latest research article, "Complement activation is associated with disease severity in multiple sclerosis," published in Neurology: Neuroimmunology & Neuroinflammation authored by our esteemed team of researchers Johanna Oechtering, Sabine Schädelin, Jan Lünnemann and Jens Kuhle.

This study shows that the activation of the complement system, a component of the innate immune system, is significantly heightened in the cerebrospinal fluid (CSF) of individuals with a clinically isolated syndrome (CIS) and MS. Additionally, it has demonstrated a strong association between increased complement activation and the presence of an intrathecal IgM production.

It also uncovers a compelling correlation between elevated complement activation levels within the CSF and key clinical parameters including Expanded Disability Status Scale (EDSS) scores, future Multiple Sclerosis Severity Scores (MSSS), and Neurofilament Light (NfL) levels. These associations support the notion that complement activation may play a pivotal role in the pathology and progression of MS.

What does this mean for the future of MS treatment? This research suggests that complement inhibition could represent a novel and promising therapeutic target to mitigate disease activity and severity. By targeting complement activation, we may unlock new avenues for more effective MS management and ultimately improve the quality of life for individuals living with this challenging condition.

Congratulations to the dedicated @RC2NB team of researchers for their unwavering commitment to advancing science and making a meaningful difference in the lives of MS patients.

Read full article here.

Last week, the Department of Clinical Research organized a Clinical Research Day to showcase the latest achievements in clinical research. The event aimed to highlight the work of the department's talented researchers, including some of our very own RC2NB team comprising Perrine Janiaud, Jens Kuhle, Lars Hemkens and Özgür Yaldizli. One of the standout talks during the event was presented by Perrine Janiaud, shedding light on significant progress in Multiple Sclerosis (MS) research.

Talk Summary: Leveraging sNfL for Personalized MS Care

Perrine discussed using serum neurofilament light chain (sNfL) as a sensitive marker for neuronal damage in MS. This marker provides valuable insights into disease activity and treatment response, offering a promising avenue for tailoring treatment decisions to individual patients with MS.

Through a Delphi study involving international MS experts and patient consultants, a consensus was achieved on treatment escalation, switching, and de-escalation algorithms based on sNfL levels. This consensus marks a significant step towards more personalized care for individuals with MS.

The next phase involves implementing these algorithms in a randomized pragmatic clinical trial known as the MultiSCRIPT trial. This trial is embedded within the Swiss MS cohort and assesses the benefits of 6-monthly sNfL monitoring compared to usual care. The trial aims to provide further evidence and insights into the potential advantages of incorporating sNfL monitoring into routine clinical practices.

Stay tuned for more updates on the MultiSCRIPT trial as the RC2NB team continues its efforts to advance personalized care for individuals with MS. The strides made in this research not only contribute to the scientific understanding of MS but also hold the promise of improving the lives of those affected by this complex neurological condition.

Image: Perrine Janiaud presenting during the DKF Clinical Research Day

RC2NB is starting 2024 strong with the publication of a new scientific article that sheds light on the world of pragmatic trials and their crucial role in providing real-world evidence for treatment decisions in Multiple Sclerosis (MS).

The study led by Julian Hirt, Perrine Janiaud, Özgür Yaldizli, Ludwig Kappos, Cristina Granziera and Lars Hemkens aimed to discover the landscape of pragmatic clinical trials in multiple sclerosis (MS) with this systematic overview led by the Pragmatic Evidence Lab (https://pragmatic-evidence.org/) at RC2NB. A comprehensive analysis was conducted on 48 pragmatic trials from 1967 to 2022, examining their characteristics, demographics, and interventions.

The article emphasizes the urgency for the scientific community to come together and leverage the untapped potential of pragmatic trials in providing meaningful, real-world evidence for the advancement of MS treatment strategies. This research is a call to action to conduct more pragmatic trials and utilize routine data infrastructures for better results.

Do you want to know more? Check out the publication  here 

Dear Friends, Colleagues, and Supporters,

As 2023 comes to a close, we would like to take a moment to wish you and your loved ones a very happy Holiday Season.

Our objective is to advance neuroscience and enhance the quality of life for people suffering from Multiple Sclerosis and other neuroimmune diseases. We are proud to say that we have made significant progress in this direction, and we could not have done it without your invaluable support. We are deeply grateful to you all, and we thank you from our hearts.

Once again, we wish you Happy Holidays, and we are eagerly looking forward to the upcoming year 2024!

Warmest regards,

Your RC2NB Team

A recent study titled "Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis" has been published in the prestigious Journal of the American Medical Association (JAMA) Neurology. The study, led by researchers Dr. Alessandro Cagol, Prof. Cristina Granziera, and Prof. Ludwig Kappos contributes to the field of neurology by providing clinicians with better tools and insights for more accurate differentiation of multiple sclerosis (MS) from other neurological conditions that exhibit brain lesions on magnetic resonance imaging (MRI).

The study analyzes data from 1051 participants from 14 European centers within the MAGNIMS consortium. The participants included those with a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions associated with white matter lesions.

This research has set a major milestone in the diagnosis of MS as it provides strong evidence for the diagnostic use of these specific biomarkers for MSTo explore the diagnostic performance of Cortical Lesions (CLs) and the Central Vein Sign (CVS), in isolation and in combination was investigated for various cutoffs. A random forest model was used to rank the diagnostic importance of CLs and CVS compared to conventional MRI features, such as the presence of infratentorial, periventricular, and juxtacortical white matter lesions (WMLs).  The results indicated that both CVS and CLs exhibited superior performance in comparison to conventional MRI features, aiding in the diagnosis of MS. The diagnostic performance of the CVS exceeded that of CLs and was increased when combining these two markers.

For more details, please refer to the full publication here.

Professors Tobias Derfuss, Christian Münz, and Burkhard Becher have received the Swiss National Foundation (SNF) Sinergia Grant for their research proposal on the role of B cells and EBV infection on Multiple Sclerosis. The interdisciplinary team of researchers from the University of Basel/University Hospital Basel and the Institute of Experimental Immunology Zurich, aim to investigate the mechanism by which Epstein Barr Virus (EBV) infection on B cells contributes to the formation of inflammatory lesions in the central nervous system (CNS) that cause symptoms of Multiple Sclerosis (MS).

The interdisciplinary team will use a systematic approach to study infected and non-infected B cells from MS patients and conduct hypothesis-driven experiments using a preclinical model with reconstituted human immune systems (humanized mice). The experiments seek to answer questions about the effects of EBV infection on the phenotype and function of circulating B cells, the impact on the response of autoreactive B cells when they encounter self-antigens, and if such virus-specific, infected or autoreactive B cells present myelin antigens to T cells to promote CNS autoimmunity.

This research, made possible by the Sinergia grant, will promote interdisciplinary collaboration and could lead to a better understanding of the causes of MS, potentially leading to new treatment options.

This prestigious recognition is awarded to influential researchers worldwide who have demonstrated significant impact in their fields of research. The selection process for the Highly Cited Researchers list is rigorous, relying on data from the Web of Science citation index and analysis conducted by bibliometric experts and data scientists at the ISI at  Clarivate.

Read the full article here

We are extremely proud to share that  Professor Tobias Derfuss has been named an Honorary Member of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). This is a prestigious recognition that was officially announced during the ECTRIMS Congress in October 2023.

Prof. Derfuss's outstanding contributions to the field of Multiple Sclerosis and his dedicated service to the ECTRIMS over the years have earned him this well-deserved recognition. During the award ceremony at ECTRIMS 2023, Dr. Mar Tintoré, the ECTRIMS President, presented Prof. Derfuss with the award.

Prof. Derfuss has been a member of the ECTRIMS Executive Committee for eight years, from 2014 to 2022, serving as a treasurer, secretary general, and member. His dedication and leadership have made a significant impact on the ECTRIMS and MS community.

We are thrilled to celebrate this remarkable achievement with Prof. Derfuss and extend our heartfelt congratulations to him!

Image: Prof. Tobias Derfuss (right) and Dr. Mar Tintoré (left), ECTRIMS president, who presented him with the award.

We are excited to share the findings of a comprehensive study that sheds light on the safety and effectiveness of ocrelizumab in treating relapsing-remitting multiple sclerosis (RRMS) over an extended period. This is the longest follow-up study of ocrelizumab-treated patients with RRMS, spanning from 2008 to 2020.

The study confirmed the sustained efficacy of long-term ocrelizumab, with no new safety concerns identified. It's remarkable to note that even after longer interruptions of 6-month dosing cycles, most participants still maintained a reduced level of disease activity, and there was no evidence of rebound.

These findings offer hope to individuals living with RRMS, bringing us one step closer to enhancing their quality of life. With ocrelizumab's proven safety and effectiveness over an extensive follow-up period, we remain confident about its positive impact on the future of MS treatment.

Read full article here

Research project of the University of Basel and the University of California San Francisco published in “JAMA Neurology”.

Basel / San Francisco, 6th November 2023

Neuroscientists of the EPIC-Team (Expression, Proteomics, Imaging, Clinical) at the University of California San Francisco (UCSF) led by Ahmed Abdelhak, MD, and of the Swiss Multiple Sclerosis Cohort (SMSC) of the University of Basel under the leadership of Professor Jens Kuhle have conducted a study in multiple sclerosis (MS) patients that demonstrates that injury to the central nervous system can be detected up to 26 months before deterioration of neurological functions manifests clinically. The results of this study will be published in the renowned journal "JAMA Neurology" on November 6, 2023.

Neurofilament Light Chain (NfL) levels in the blood is a specific biomarker for damage of nerve cells and has been established earlier for monitoring acute disease activity and the efficacy of therapy. However, there was no biofluid marker defined that associates with continuous worsening of neurological functions, called 'progression', that occurs despite optimal therapy in most MS patients. The key finding of this study is that increased levels of NfL prognosticate progression in a period when it cannot be diagnosed with current clinical tools. This advance in early detection of disease course opens new treatment windows and better management of MS.

The study conducted by UCSF and University of Basel researchers aimed at addressing the current diagnostic gap in predicting disease progression in MS by analyzing long-term data from nearly 13,000 patient visits and blood samples. "The result that blood levels of NfL can prognosticate disease progression up to more than two years in advance of the occurrence of clinical manifestation of symptoms is a game changer for how we can monitor and manage the treatment of MS patients: it provides crucial rational for early therapeutic interventions," said Ahmed Abdelhak, the first author of the study.

The study demonstrates that NfL concentrations increase sharply between 12 and 26 months before the diagnosis of confirmed disability progression is made. Once the disability becomes clinically evident, NfL concentrations are no longer elevated compared to patients with stable disease, suggesting that this biomarker shows dynamic changes indicative of actual disease processes. This suggests that NfL measurements indicate underlying nerve injury earlier than physical examinations of neurologists. Overall, these findings can help doctors and clinicians identify patients who are at high risk of progression and provide early therapeutic intervention to contain disease progression.

Relevance for MS-Research

This study combines two of the largest and best documented MS cohorts worldwide. It builds on earlier work conducted by researchers from the University of Basel that were published in February 2022 and September 2023 in “Lancet Neurology”. The Swiss researchers demonstrated therein the added value of NfL as a blood biomarker for assessing the disease activity state of MS patients by establishing normative data for this biomarker in adults and children that allows to qualify NfL concentrations as normal or increased.

„Besides the groundbreaking insights regarding the temporal link between NfL elevation and disease progression in MS, the study reinforces the pivotal role of NfL as an early marker of neuronal injury. Monitoring NfL levels has already been established as an important indicator to detect concurrent disease activity with higher sensitivity than a clinical examination or conventional MRI scans. The current study further stresses the critical value of NfL measurement for a more personalized medical treatment”, says Professor Jens Kuhle.

The focus of future studies is how the new insights on what increased NfL means can be translated into better treatment algorithms.

Relevance for MS Patients

Nearly three million people worldwide suffer from MS. Every progress in the understanding of this disease has the potential to improve therapy efficacy, and hence the lives of patients as well as their families. Early and precise detection of prospective damages opens new windows of early therapeutic intervention. The therapeutic target is to hold NfL concentrations at levels of healthy persons.

Read full article here 

Background

Multiple sclerosis (MS) is the most common immunological disorder of the nervous system (> 1 in 1000). This disease has a strong female preponderance and is the most common cause of permanent disability in young adults. MS affects the central nervous system causing a variety of neurological symptoms escalating disability over time. Despite the availability of a large panel of approved disease-modifying MS drugs, frequently physicians lack data-based support to prescribe the most effective treatment at a given time point along the patient pathway, highlighting the need for personalized clinical management. Artificial intelligence (AI)-driven solutions hold a high potential for precision medicine but have not yet fulfilled expectations. Thanks to a trans-regional collaboration between institutions from four countries (Switzerland, Germany, France, and, Luxembourg), CLINNOVA has the mission to support the digitalization of healthcare, unlock healthcare’s AI potential, and improve personalized treatments of chronic inflammatory diseases. The CLINNOVA consortium focuses on 3 Use Cases of immune-related diseases with large unmet medical burden: multiple sclerosis, inflammatory bowel diseases and, rheumatoid diseases.

Research Question

CLINNOVA-MS aims to build a prospective MS patient cohort across the participating clinical centers to generate structured, standardized, interoperable, quality-controlled, multi-sourced, and multi-dimensional data. These data will be analyzed in a federated learning platform to train and develop AI-algorithms generating personalized therapy solutions for patients, identify characteristics associated with early MS and transitioning phases to progressive MS, and validate digital biomarkers allowing a continuous monitoring of those patients.

Study Methodology

CLINNOVA-MS is a prospective cohort study including participants with early MS or in the transitioning phase to progressive MS. Up to 100 participants will be enrolled in the study in Basel and an equivalent number should be also enrolled at each participating center.Eligible patients will be asked to provide data and samples and will be followed up for 5 years starting from the date of inclusion. Patients reported outcomes and cognitive and motor assessments will be performed using the Healios+Me smartphone application. Biological samples (i.e., blood, cerebrospinal fluid, and stool) as well as imaging data (if performed as per standard of care) will be collected locally, then processed and analyzed centrally at the appropriate partner institutions. The sample-associated data, monitoring data collected via the digital application and patient visits data will be analyzed through a privacy-preserving platform using federated learning. This approach allows to train algorithms on datasets from different clinical sites without sharing sensitive data.

Significance of the study

Thanks to its consortium, CLINNOVA-MS will make a significant step forward to facilitate early MS detection, enable personalized medicine approaches through AI‐based stratification, and improve patients’ care and quality of life while reducing healthcare costs.

Contributors

Prof. Ludwig Kappos (RC2NB, USB)
PD Dr. Lars G. Hemkens, MPH (RC2NB, USB)
Dr. Bebeka Cosandey (RC2NB, USB)
Dr. Amandine Bovay (University of Basel)
Dr. Bram Stieltjes (University Hospital Basel)
Dr. Thierry Sengstag (University of Basel)

Read Full DKForum Article Here (German)