On October 29, 2024, we hosted the Scientific Advisory Board (SAB) Meeting at Biozentrum, University of Basel. It was a moment to reflect on a year of progress, research, and collective effort in advancing multiple sclerosis (MS) research.

A heartfelt thank you to our dedicated speakers and the entire team who showcased their work through engaging presentations. The feedback from our Advisory Board was immensely positive, emphasizing their encouragement for the strides we've made in translational research.

What sets RC2NB apart is the unique research environment in Basel. Here, a powerful combination of well-defined patient cohorts, a strong clinical trial framework, and advanced tools for clinical phenotyping converge seamlessly. Add to that our state-of-the-art neuroimaging techniques, biomarker analysis, and precise immunological monitoring of therapies, and you have a setting primed for advancements.

This meeting reinforced what we already knew: impactful research thrives where expertise, technology, and dedication meet. Thank you to everyone who participated, contributed, and made this milestone possible.

Looking forward to more research and continued innovation in the year ahead!

Have you heard about Federated Learning? It’s transforming MS care - right from Basel! 

We’re excited to announce the latest publication from Clinnova. In this cross-border initiative, Dr. Bram Stieltjes and his team lead the Data Architecture, with Prof. Cristina Granziera spearheading Clinnova’s overall efforts in Switzerland. Clinnova, uniting France, Germany, Switzerland, and Luxembourg, is pushing the boundaries of precision medicine by advancing data federation, standardization, and interoperability across Europe - and Basel is at the core of this mission.

So, what’s Federated Learning (FL)? It’s a powerful AI approach that allows institutions to collaboratively develop models while keeping sensitive data secure at each location. This approach is transformative for complex diseases like Multiple Sclerosis (MS), enabling us to create predictive models that detect disease progression, optimize treatment pathways, and validate digital biomarkers without compromising patient privacy.

Our new publication details Clinnova’s first Federated Learning proof of concept (POC) for MS. In partnership with the IHU Strasbourg, the POC uses FL for MRI image segmentation in MS, a method that serves as a foundation for future AI-driven healthcare advancements. Clinnova’s work also spans inflammatory bowel disease and rheumatoid diseases, with plans for federated biobanking and a digital health innovation platform, bringing data-driven care to the forefront.

Dive into the full publication to discover how Federated Learning, driven by our Basel team, is shaping a new era of secure, high-quality data sharing and collaboration for MS and beyond. 

Read Full Article: https://arxiv.org/pdf/2410.02443 

A post-hoc analysis of data from 13 clinical trials, including 6155 patients treated with OCR, revealed key insights on infection risks in patients with multiple sclerosis (PwMS). Over a median treatment period of 3.7 years, 6.8% of patients experienced serious infections (SIs), with the most common being respiratory, urinary, abdominal, gastrointestinal, and skin infections. Most cases (~90%) resolved, and treatment continued in over 80% of patients. Significant risk factors for SIs included the presence of comorbidities, high EDSS scores, and recent relapse activity, while time on OCR was not significantly associated with an increased risk of infections. The findings suggest that continuous treatment with OCR shows a manageable infection profile, and addressing modifiable risk factors may further reduce infection risks.

We would like to congratulate the entire team for this important contribution to multiple sclerosis research, and a special shout-out to our very own Prof. Ludwig Kappos and Tobias Derfuss from RC2NB for their significant contributions to this study!

Full article: https://journals.sagepub.com/doi/10.1177/17562864241277736 

Hot off the press!

We are thrilled to announce the publication of our article, "Advanced MRI Measures of Myelin and Axon Volume Identify Repair in Multiple Sclerosis," in the @Annals of Neurology.

This study utilizes advanced MRI  techniques to examine the repair and damage processes in multiple sclerosis (MS) lesions. The research involved the analysis of 128 MS patients and 72 healthy controls, revealing that both repair and damage processes occur across the disease spectrum. Importantly, the frequency of repair lesions was found to be correlated with lower disability and neuroaxonal damage, underscoring the potential of MRI in monitoring lesion activity and guiding personalized treatment strategies.

This work underscores the potential of MRI and AI-driven analysis in tracking lesion changes, which could lead to more personalized MS treatments. A big shoutout to the entire team for their innovative contributions, especially Gretel Sanabria Diaz and Cristina Granziera, for their exceptional efforts in advancing MS research.

Access the full article here: https://onlinelibrary.wiley.com/doi/10.1002/ana.27102 

📢 Our Team is Growing!!! We’re excited to announce the newest additions to the RC2NB team, bringing fresh perspectives and specialized expertise to fuel our cutting-edge research!

Join us in welcoming:

Tanja Stoll, Study Nurse

Tanja completed her Master’s degree in Molecular Nutritional Science in April 2024, specializing in clinical research. During her research internship in the USA, she gained valuable experience in both human studies and laboratory work. Currently a Study Nurse at RC2NB, Tanja is responsible for preparing and conducting study days, as well as processing biological samples. She is excited to be part of an innovative research team, contributing to cutting-edge research.


Lukas Schönenberger, PhD Candidate

Lukas completed his medical degree at the University of Basel in September 2024 and is now an MD-PhD student with the ThINk group. His research focuses on ultra-high spatial resolution MRI and molecular characterization of remyelinating lesions in Multiple Sclerosis, primarily within the postmortem section. Lukas is eager to advance his understanding of neurodegenerative diseases at the molecular level through his work.

Louise Chaboud , PhD candidate

Louise, with a background in emergency medicine and critical care nursing, pursued a Master’s degree in Comparative Effectiveness Research at Université Paris Cité. During her master's internship at Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), she focused on decentralized clinical trials, conducting systematic reviews and meta-analyses. Now a PhD candidate, Louise's research centers on developing novel endpoints in multiple sclerosis to improve patient outcomes.

Jonathan Salfati, Data Manager

Jonathan has an extensive background in data management with 15 years of expertise in information technology, supporting clinical data management in various projects. He has contributed to the technical build of the Swiss MS Cohort (SMSC) since 2013 and the MultiSCRIPT trial since 2023. Before joining RC2NB, he optimized data processes and implemented data strategies at various institutions, focusing on advancing research through efficient data management solutions.

With their talents, we're pushing the boundaries of what’s possible. Help us give them a warm #welcome as we continue to grow!
 

We successfully concluded ECTRIMS2024! 🎉 The wide range of presentations and poster sessions from the Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) highlighted the exciting advancements in MS research. These included cutting-edge imaging techniques and the latest developments in machine learning and deep learning applications. Innovative approaches to understanding MS progression, lesion classification, and digital health solutions were also showcased. The energy throughout the event was inspiring, and there were incredible discussions.

We are proud to have had a strong presence at this year’s event with over 50 talks and poster presentations, showcasing cutting-edge research and innovation in multiple sclerosis research.

A big thank you to everyone who contributed to making this year’s event unforgettable. We're already looking forward to next year’s conference in Barcelona, ECTRIMS!

Exciting week ahead as the Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), ThINK, and Indivi teams head to ECTRIMS in Copenhagen, 18-20 September 2024. We are proud to have a strong presence at this year’s event with +30 talks and poster presentations showcasing cutting-edge research and innovation in multiplesclerosis research.

Be sure to attend the spotlight sessions by our very own key speakersCristina Granziera and Ludwig Kappos, who will share their expertise with the global MS community We look forward to connecting with the MS community, sharing knowledge, and driving the future of MS care together!
 

RC2NB is pleased to share significant progress in the MultiSCRIPT Trial. Despite the summer break, our recruitment efforts have remained strong, and we have successfully enrolled 373 participants, an impressive 40% of our target sample size.

We are also delighted to welcome two centers that recently joined the MultiSCRIPT initiative: Inselspital and Zurich University Hospital. Their involvement marks a valuable expansion of our collaborative efforts.

The ongoing success of the MultiSCRIPT Trial highlights the effectiveness of integrating research seamlessly into the routine care provided by SMSC. This approach streamlines the research process and generates high-quality evidence that directly informs clinical decision-making.

This achievement would not be possible without the unwavering dedication and hard work of our SMSC physicians, study coordinators, and nurses and most importantly the commitment of our participants.

To stay updated on our progress and learn more about how MultiSCRIPT is shaping the future of care, visit our website: https://multiscript.rc2nb.ch. Join us on this journey of discovery and innovation!

Thank you for being an essential part of this journey.

RC2NB is incredibly proud to announce that Elisabetta Giacomelli has been awarded the Best Master’s Thesis 2024 during the Department of Biomedical Engineering Research Day! Elisabetta’s thesis, titled “Identification of 9.4T MRI Sequences for Enhanced Cellular Visualization of Multiple Sclerosis Lesions,” has been recognized for its innovative research.

Elisabetta’s work focuses on the potential of ultra-high-field MRI (9.4T) to improve the visualization of Multiple Sclerosis lesions, offering new insights into the mechanisms of damage and repair in this complex neurological disorder. Her research not only showcases technical excellence but also a deep commitment to advancing our understanding of MS, which has the potential to impact future diagnostic and treatment strategies.

This award is a testament to Elisabetta's hard work, dedication, and innovative approach to her research. We are thrilled to see her efforts recognized and have her as part of our team.

Congratulations, Elisabetta, on this well-deserved honor! We look forward to seeing all the amazing things you will continue to achieve.

Image: Prof. Pablo Sinues and Elisabetta Giacomelli 

At RC2NB, our mission is to push the boundaries of science and healthcare through cutting-edge research and innovation. As part of University Hospital Basel (USB), we know that our greatest achievements come from the synergy of diverse talents and perspectives working together.

Diversity in our team isn’t just a value, it’s the driving force behind our innovation. Each member of RC2NB brings unique experiences and expertise that spark fresh ideas and new approaches to solving the complex challenges in healthcare. This blend of talent and diversity empowers us to lead in research and deliver impactful healthcare solutions.

RC2NB is proud to be part of #GenerationUSB campaign, at University Hospital Basel, which celebrates the dynamic and forward-thinking community that makes USB a leader in medicine. Our collective commitment to diversity and excellence in research fuels the innovations that shape the future of healthcare.

Together, RC2NB and USB are more than just institutions, we’re a generation united by the pursuit of scientific excellence and driven by the diverse talents that make it possible.

Join us in celebrating the power of diversity and talent as we continue to innovate for a healthier future!

Image: Aida Suljakovic & Dr Bebeka Gjoksi Cosandey, who exemplify the exceptional talent and dedication that drive #RC2NB success.
 

Read the full article here!

New Study Announcement: Face Masks for Respiratory Symptoms

A new study published in BMJ (July 2024), co-designed by Prof. Lars Hemkens from RC2NB, assessed if wearing surgical face masks in public spaces reduces self-reported respiratory symptoms. The decentralized pragmatic randomized trial, conducted entirely online and remotely in Norway, included 4,647 adults and leveraged routinely collected “real world” data.

The study found that 9% of mask wearers reported symptoms over a 14-day period versus 12% of those not wearing masks, a statistically significant difference.

The innovative design of the study and related discussions offer valuable insights into ongoing debates around patient-reported outcomes, decentralized trials, remote assessment, and the challenges of missing data in non-blinded real-world research.

These discussions are especially important for our upcoming studies, as we expect to face similar challenges. The approach and outcomes of the study will influence the design and methodology of these projects, leading to stronger and more reliable results even when routine data from public registries is not available.

Read full article here: https://www.bmj.com/content/386/bmj-2023-078918

We are excited to share some fantastic progress in our MultiSCRIPT recruitment efforts!

As we reach the sixth month of our recruitment phase, we are pleased to announce that the team in Lugano has successfully recruited their first patient to the MultiSCRIPT study. This marks a significant milestone, and we extend our warmest congratulations and heartfelt thanks to the dedicated Lugano team for their hard work and perseverance.

As of July 5, 2024, we have recruited a total of 286 SMSC participants to the MultiSCRIPT study. This impressive figure represents over 30% of our target recruitment, achieved in just five months. This accomplishment is a testament to the relentless efforts of all our recruiting physicians and the incredible commitment of the SMSC participants. We are deeply grateful to each of you for your contributions and dedication.

We would like to give special recognition to Chiara Zecca, Claudio Gobbi, and Giulio Disanto for their unwaverYour efforts have been instrumental in driving our success so far.

Looking ahead, we will continue to initiate other centers throughout the summer, expanding our reach and furthering our recruitment goals. As we progress, we remain committed to advancing our research and making meaningful strides in our study.

Stay tuned for more updates as we continue our journey with MultiSCRIPT.

On May 30, 2024, to mark World Multiple Sclerosis Day, Prof. Cristina Granziera was the focus of an insightful interview on radio SFR1. During this comprehensive discussion, Prof. Granziera was invited as a leading expert in the field, and shared valuable information about the complexities of Multiple Sclerosis (MS), shedding light on its multifaceted nature.

Key Highlights from the SFR1 Interview:

Advancements in Diagnosis: Prof. Granziera explained that MS is an autoimmune disease where the immune system attacks the myelin layers in the brain. Over the past two decades, significant progress in imaging and the development of new biomarkers has improved the accuracy of MS diagnosis. This has led to an increase in the number of diagnosed cases, as more subtle signs of the disease can now be detected.

Increased Longevity and Quality of Life: One of the reasons for the rise in MS diagnoses is the improved therapies available today. Patients with MS are living longer and better lives due to these advancements, resulting in a higher number of individuals living with the condition.

Triggers and Causes: Despite intensive research, the exact cause of MS remains unknown. However, Prof. Granziera highlighted that factors such as viral infections, vitamin deficiencies (especially vitamin D), smoking, and genetic predisposition play roles in triggering MS. It is important to note that having a genetic predisposition does not guarantee that an individual will develop MS, as other environmental and lifestyle factors are involved.

Symptoms and When to Seek Medical Advice: MS is often called the "disease of a thousand faces" because its symptoms can vary widely. Common symptoms include visual disturbances, muscle weakness, dizziness, pain, and bladder disorders. Prof. Granziera emphasized the importance of seeking medical advice if any of these symptoms are experienced.

Current and Future Treatments: Currently, there is no cure for MS because the exact cause is still unknown. However, there are around 20 immunomodulating drugs available that can slow the progression of the disease and alleviate clinical symptoms.

Listen to the full interview on radio SFR1 and learn more about the ongoing fight against Multiple Sclerosis.

Listen to the original interview in German

The University Council of the University of Basel has approved the appointment of Prof. Dr. Lars G. Hemkens to a titular professorship at the Faculty of Medicine for Clinical Epidemiology.

Lars G. Hemkens, MD, MPH, is a Senior Scientist at the Department of Clinical Research, University of Basel, and leads Pragmatic Trials and Real World Evidence at the Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB). Additionally, Dr. Hemkens is affiliated with the Meta-Research Innovation Center at Stanford (METRICS; Stanford University, USA).(https://lnkd.in/ecgsCUT7)

Previously, Dr. Hemkens served as the Deputy Director of the Basel Institute for Clinical Epidemiology and Biostatistics (ceb) until its closure. He has also worked at the Stanford Prevention Research Center (Stanford University) and the Institute for Quality and Efficiency in Health Care (IQWiG, Cologne, Germany; Department of the Director). At RC2NB, he leads the workstream Pragmatic Trials and Real World Evidence and the Pragmatic Evidence Lab. (www.pragmatic-evidence.org) His research includes developing and investigating digital biomarkers and digital health applications in multiple sclerosis. Dr. Hemkens is also the Co-PI of MultiSCRIPT, a nationwide pragmatic platform trial fully embedded in the Swiss MS cohort, aimed at continuously improving care for persons with multiple sclerosis.

In his role at the Department of Clinical Research, Dr. Hemkens co-designs various clinical studies across a wide range of medical fields and closely supervises the design of nationwide investigator-initiated clinical trials. He is an associate editor and thematic series editor of “Big data for randomized trials” at the journal Trials, and serves on the editorial board of BMJ Evidence-Based Medicine and the working committee of the RECORD reporting guideline group. Dr. Hemkens also teaches comparative effectiveness research and pragmatic trial design at the University of Basel and Sorbonne Paris Cité, France.

RC2NB is honored to have  Dr. Hemkens as a valued member of our team. We support his substantial contributions and eagerly anticipate his ongoing influence in the field of clinical research, neuroscience and digital health.

Link to the University of Basel announcement: here

We are excited to share that our recent research on imaging biomarkers in multiple sclerosis (MS) has been published in Nature Scientific Reports. This collaborative project, led by Muhamed Barakovic and Cristina Granziera, investigates the potential of diffusion MRI and a new model called "soma and neurite density imaging (SANDI)" to non-invasively analyze cellularity in the cortex of individuals with MS.

Paper Key Findings:

• Overall Decrease in Cortical Cellularity: The study revealed a significant reduction in cortical SANDI form in people with MS (pwMS) compared to healthy controls, indicating global degenerative processes consistent with neuronal loss.

• Differences in MS Types: Progressive MS (PMS) showed higher SANDI fsoma in the outer cortical layer, suggesting increased innate inflammatory cells in these regions. Relapsing-remitting MS (RRMS) exhibited increased SANDI fsoma in subpial lesions, aligning with existing pathological data.

• Correlation with sNfL: A significant correlation between SANDI fsoma and serum neurofilament light chain (sNfL), a biomarker of inflammatory axonal damage, indicating a link between SANDI fsoma and inflammatory processes in pwMS.

The data emphasizes the potential of SANDI in clinical settings and its use as a biomarker for monitoring changes in cellularity associated with neurodegeneration and neuroinflammation in MS patients. This research represents a significant advancement in understanding MS pathology and in improving diagnostic and treatment strategies.
Read full article here
 

We are excited to announce the publication of an important methods guidance paper in the British Medical Journal (BMJ) titled "Guidance on Terminology, Application, and Reporting of Citation Searching: the TARCiS Statement."

Systematic literature searches form the basis of evidence-based healthcare by rigorously identifying relevant studies. While traditional term-based searching in electronic databases is well-established, citation searching has become a crucial technique to discover additional relevant evidence. However, the methodology and terminology associated with citation searching have lacked standardization for decades.

To address this gap, a four-round Delphi consensus study was conducted resulting in the development of the Terminology, Application, and Reporting of Citation Searching (TARCiS) statement. TARCiS offers 10 specific recommendations, each with a detailed rationale and guidance on how and when to conduct and report citation searching in systematic literature reviews. Additionally, the statement identifies four research priorities aimed at further advancing the methodology.

This comprehensive guidance was developed in collaboration with the medical library of the University of Basel, the Eastern Switzerland University of Applied Sciences, and an international panel of 30 experts. The TARCiS statement is expected to significantly enhance the standardization and transparency of citation searching in systematic reviews, encouraging review teams to integrate these recommendations into their workflows.

We encourage researchers, systematic review teams, and healthcare professionals to incorporate the TARCiS recommendations into their practices to improve the quality and consistency of evidence syntheses.

Read the full guidance paper in the BMJ.

RC2NB is excited to share the latest media coverage of one of our innovative international projects - Clinnova. This project focuses on revolutionizing autoimmune disease treatment through personalized medicine while ensuring data quality and protection using federated learning - a decentralized approach to AI training.

Clinnova consortium establishes Basel as the center of excellence for the region's multiple sclerosis (MS) treatment and highlights the close collaboration between our team, the University of Basel and the University Hospital Basel.  The project, led by our co-CEO, Cristina Granziera, has received CHF 4 million in funding from the Basel Canton, benefiting patients and strengthening Basel's position in the global medical research community.

Project Highlights:

Personalized Treatment: Using AI, Clinnova will analyze large volumes of patient data to tailor therapies to individual needs, enhancing treatment efficacy and reducing side effects.

International Collaboration: The Clinnova consortium ensures data quality and protection through decentralized AI training, keeping patient data within local institutions while sharing insights globally.

Innovative Approach: Federated learning led by Bram Stieltjes will enable the development of algorithms that predict the best treatment options and timing for each patient, especially crucial for diseases like MS, known for its diverse manifestations.

We invite you to join us in sharing the news about this initiative that underscores Basel's role as a hub of medical excellence and innovation. Together, we are paving the way for a future where AI and personalized medicine transform healthcare.

Read the full article written by Agelika Jacobs to learn more about this remarkable project and the future of precision medicine here

MultiSCRIPT  has recently achieved a major milestone with 1^st patient enrolled on February 5th, 2024 in Basel. Since then, over 150 participants have been enrolled and randomized in less than 3 months (anticipated recruitment is 915 participants over a 2-year period).

This is a testament that keeping things simple and fully embedded in the patient’s care contributes to a smooth recruitment. MultiSCRIPT is a pragmatic clinical trial that's embedded within the Swiss MS cohort, and it seeks to assess the benefits of 6-monthly sNfL (serum neurofilament light chain) monitoring in addition to usual care compared to usual care alone. The trial aims to provide further evidence and insights into the potential advantages of incorporating sNfL monitoring into routine clinical practices to inform more personalized strategies for multiple sclerosis (MS).

For those who are interested in learning more about MultiSCRIPT-Cycle 1, a detailed protocol is available as a preprinthttps://www.medrxiv.org/content/10.1101/2024.03.22.24304720v1

We encourage you to check it out and share it with others who might find it useful.

 We would like to express our gratitude to the study coordinators, nurses, and physicians at the MS center in Basel, whose hard work and dedication have made this achievement possible. Thank you to the Swiss National Science  Foundation for supporting this Investigator Initiated Trial.

We are also pleased to announce that we will initiate the other SMSC centers soon, including Ospedale Regionale di Lugano, University Hospital Geneva, University Hospital Lausanne, Inselspital Bern, Kantonsspital Aarau, University Hospital Zürich, and Kantonsspital St. Gallen.

If you're interested in learning more about our awesome team and contributors, we encourage you to visit the multiSCRIPT website at the following URL: https://multiscript.rc2nb.ch

We are excited about the progress and believe that MultiSCRIPT will significantly improve the lives of people with MS.

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)