The consortium name ‘MultipleMS’ refers to the disease Multiple Sclerosis, the multiple manifestations thereof and to the size and multiplicity of the partnership.In this project, universities and companies across 11 European countries and the US will unite efforts to tailor the development and application of therapies to the individual MS patient. Behind the scenes we are working on the required approvals, data transfer agreements and database solutions. In September 2020, we completed inclusion of 500 patients that will be followed over at least two years, whilst analysis of already existing data across centres is in advanced stages.
Pernilla Stridh presenting the progression GWAS study on behalf of the IMSGC and MultipleMS at the Nordic Society of Human Genetics and Precision Medicine in Tallinn.
A new study in Nature by The International Multiple Sclerosis Genetics Consortium (IMSGC) and The MultipleMS Consortium has identified the first genetic variant associated with disease severity in multiple sclerosis. The finding opens the door to the development of treatments that fight disease progression – a great unmet need facing people with MS.
The new genome-wide association study of more than 22,000 people with multiple sclerosis points to a genetic variant that increases disease severity. “Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years,” said Sergio Baranzini, a professor of neurology at UCSF and co-senior author of the study.
“Understanding how the variant exerts its effects on MS severity will hopefully pave the way to a new generation of treatments that are able to prevent disease progression,” said Stephen Sawcer, a professor at the University of Cambridge and the other co-senior author of the study.
The variant sits between two genes called DYSF and ZNF638 with no prior connection to MS. “These genes are normally active within the brain and spinal cord, rather than the immune system,” said Adil Harroud, MD, lead author of the study and former postdoctoral researcher in Baranzini’s Lab and now affiliated to Karolinska Institutet. “Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies.”
“This is a breakthrough finding because it provides the first real progress in understanding long-term disability in MS, where patients gradually lose their mobility and independence,” says Ingrid Kockum, professor at Karolinska Institutet, and principal investigator for the European part of the study.
The work was the result of a large international collaboration of more than 70 institutions from around the world, where two large MS research consortia joined forces: The International Multiple Sclerosis Genetics Consortium (IMSGC) and The MultipleMS Consortium.
This work was supported in part by funding from EU’s Horizon 2020 (MultipleMS project, coordinated by Ingrid Kockum, Karolinska Institutet) and the NIH/NINDS (R01NS099240, coordinated by Sergio Baranzini, UCSF, and Stephen Sawcer, University of Cambridge).
Research Briefing: https://doi.org/10.1038/d41586-023-01787-3
Publication: “Locus for severity implicates CNS resilience in progression of multiple sclerosis”, International Multiple Sclerosis Genetics Consortium, MultipleMS Consortium (see the paper for a complete list of authors), Nature, online 28 June 2023, doi: 10.1038/s41586-023-06250-x.
Source: UCSF & Karolinska Institutet
In conjunction to hte ECTRIMS 2022, MultipleMS held its annual general assembly in Amsterdam. The meeting offers a prospect of many analysis reaching the dissemination and publication phase. We will continuously highlight publications from the MultipleMS consortium in the next phase of our consortium.
The global outbreak ofCovid-19 has had an impact on all medical activities across the world, including at theMultipleMS inclusion- and follow up centres. At the majority of our inclusion centres, new routines are in place to warrant the safety of both patients and researchers. Our studies proceed as close to the original planning as feasible, whilst the analyses and discussions of these are now mainly performed using remote tools. In spite of delays caused by the acute phase of the global outbreak, we remain dedicated to reaching our study end points. We refer our study patients to their respective inclusioncentres for an up-to-date overview of the local routines.
In January2018, the MultipleMS consortium included the first patients in an extensive andambitious prospective study across multiple European study centers. In September2020, the goal of 500 required patients was reached. This is a major milestonein our project, and whilst the first patients in this prospective study havealready completed their24-month follow up visits, in two years from today theprospective study is concluded with the last 24-month visit. In the meantime,the consortium is working hard to extend the follow up of included patients,since this is valuable and important data. Several initiatives are launched tofund a 36-month follow up, and hopefully additional future visits.
In parallelwith our prospective study mentioned above, several other projects are advancingin which researchers across the consortium are analyzing already existing data collectedfrom all participating and collaborating clinical centers.
In the photo the current coordinators of the prospective study from "The Technical University of Munich, Germany"
The global outbreak ofCovid-19 has had an impact on all medical activities across the world, including at theMultipleMS inclusion- and follow up centres. Nevertheless, the prospective study is currentlyfollowing its projected course, with only minor delays for visits that were planned duringthe acute phase of the pandemic. Each centre has its own local guidelines under which the patients' follow up is secured and safe.
The yearly general assemble meeting is ongoing in Stockholm. A large part of the active collaborating parties in MultipleMS is presenting their status updates and future plans. Most of the participants will continue this week with the yearly ECTRIMS conference.
We have finally received all required approvals to start collecting newly diagnosed patients. On the 8thof January 2018 the first Norwegian MSpatient was included in the prospective cohort, which is at the core of the entire project. We will continue to collect at our inclusion sites across Europe until we reach a cohort of 500 newly diagnosed patients, all of whom will be followed closely with our harmonised protocols for data collection.
“We believe that multiple sclerosis (MS) can be beaten. We are a diverse group of scientists and physicians with a common goal: to improve the lives of people with MS. In theMultipleMSproject, we will weave together the unique medical histories of each person with MS to paint a detailed molecular portrait of the disease. Over the next five years we will use this molecular portrait to develop new ways to stop the disease in its tracks and develop protocols for choosing therapies for each individual patient” The MultipleMS consortium
“As innovation advisor in MultipleMS, I am keen to help connecting bright people with bright ideas and create an innovative, trusted, and inspiring environment to bring those ideas to life.” Wouter Jansen, Innovation Manager of MultipleMS, PwC
“InMultipleMSwe have a unique opportunity to develop and apply powerful algorithms for integrating rich data from DNA to patient records, enabling a more personalized and preventive approach for patients suffering from Multiple Sclerosis” Jesper Tegnér, Chaired Strategic Professor in Computational Medicine, YouHealth (Sweden).
“We take on the hardest and most pressing problems in human disease, and bring whatever resources and methods are required to bear on them. We consider our inability to predict an individual’s disease course and response to therapy in MS unacceptable, and participate in theMultipleMSproject to solve this problem.” Chris Cotsapas, Associate Professor of Neurology and of Genetics (Yale University School of Medicine, USA)
“Although we live in the information age, integration and contextualization of this information has consistently been realized at a much slower pace in the healthcare space than in financial, consumer or retail industries. This is due in part to the enormous complexity of the biological systems underlying the human body, but also due to the lack of standardization and cooperation across research teams doing similar work.MultipleMSis an important step in that direction and it will provide a platform for researchers and patients with MS to advance personalized medicine together”
Sergio Baranzini, Professor at UCSF, USA.
“As a neurologist I regularly meet persons suffering from MS, who I aim to treat and help in the best possible way. By contributing to this cutting edge MultipleMS research project, I hope we will bring this field an important step forward. This project allows us to analyze multiple facets of MS in close collaboration with well-established successful consortia and excellent researchers worldwide, giving us a great opportunity to exploit and implement novel research to the best of our patients, their families and other stakeholders."
Hanne Flinstad Harbo, Professor of Neurology, University of Oslo/Oslo University Hospital
“I have always been fascinated by the complexity of the human body and how devastating the consequences of tipping a balance between a myriad of functions can be. Understanding this complexity, no matter how challenging, is the only way to truly make a difference for people who suffer from debilitating diseases such as MS. This is what MultipleMS is for me.”
Maja Jagodic, Karolinska Institutet, Sweden.
“I am excited about theMultipleMSproject since I think that we will be able to address research questions that we have not been able to address efficiently previously through collaboration between researchers with unique experiences and because we are utilizing data from different fields in joint analyses.
"I am motivated to carry out this project because I believe that it will result in real progress in understanding aspects of Multiple Sclerosis pathogenesis which can be used for improvement of treatment of Multiple Sclerosis.”
MultipleMS is funded by the European Union under the Horizon 2020 programme, grant agreement 733161. The contents of this website are the sole responsibility of the MultipleMS project and do not necessarily reflect the views of the European Union.
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