Multiple sclerosis (MS), an inflammatory disease of the central nervous system, affects more than 1 million people in Europe and an estimated 2.8 million worldwide. MS is characterized by an inflammation-related loss and damage of the myelin layer in the brain and spinal cord, which insulates the nerves – potentially leading to serious consequences such as paralysis or severe visual impairment.
The cause of this damage is not known. Viral infections, particularly with the Epstein-Barr virus, have been suspected for years. However, this link was difficult to prove, as up to 95% of all people become infected with EBV in the course of their lives while MS is considered a relatively rare disease. It was not until 2022 that an US research group achieved a breakthrough - by evaluating the viral status and MS diagnoses of an incredible 10 million US military personnel.
"The researchers found that MS is 30 times more common among those infected with EBV than among people who have never been in contact with this virus - this is extremely strong evidence that the virus is causally involved in the disease," explain Catarina Veroni and Roberta Magliozzi, two neuropathologists specialized in MS. "This result was an important clue for us to be able to plan further research projects."
MS can be treated better and better. However, the currently available therapies that mainly target the immune system are not always effective, and for many people living with MS a severe course with increasing physical limitations cannot be halted." We need therapies that attack the disease to their roots. We need to understand how EBV induces the development of MS in the first place. To this end, we need more precise models to investigate the interaction of the viruses with their host cells. There are many questions that remain unanswered. For example, we don't even know whether the immune cells of people affected can even efficiently reduce EBV-infected cells? Or does this attempt to control the pathogen lead to an overactivation of the immune system, which ultimately triggers autoimmune reactions? And which viral antigens play a role in this?" ask the immunologists Christian Münz, Jens Geginat, Josef Mautner and Marvin van Luijn.
To answer these questions, the EU is now funding the international "BEHIND-MS" consortium under the leadership of the DKFZ as part of its HORIZON Europe research funding programme A total of twelve partner institutions from six European countries are participating in the consortium. The interdisciplinary team aims to develop new cell and animal models in which the interactions of viruses, immune cells and nerve cells can be followed in detail under conditions that are as close to nature as possible comment Marc Thier, Susanne Delecluse and Henri-Jacques Delecluse who will combine their respective expertise in Neurobiology and Virology to tackle the disease.
The researchers then want to use these systems to test various hypotheses on the development of the disease, including theories that do not focus solely on the role of the immune system. The search for genetic or infectious co-factors that promote the disease will also be part of the research program. This should make it possible to identify people with a particularly high risk of developing the disease. The consortium will also make extensive use of artificial intelligence and statistical methods and includes the physicists Alessandro Taloni and Francis Farrelly.
"Ultimately, our goal is to identify biomarkers that signal specific stages or progressions of the disease and thus arrive at new, more precise therapeutic approaches. In this way, we hope to halt the cruel course that the disease takes in many cases," say the neurologists Jan Lünemann and Manuel Comabella Lopez.
This research holds the promise of advancing our understanding and treatment options for MS, thereby bringing us closer to enhancing the quality of life of people with MS."
Elisabeth Kasilingam, CEO of the European Multiple Sclerosis Platform
The funding for BEHIND-MS amounts to a total of 7.1 million euros over five years.
The partners in the BEHIND-MS consortium are
- German Cancer Research Center (DKFZ), Coordinator (Germany)
- Istituto dei Sistemi Complessi - Consiglio Nazionale delle Ricerche (Italy)
- Erasmus MC, University Medical Center Rotterdam (Netherlands)
- Helmholtz Center Munich (Germany)
- Istituto Superiore di Sanità (Italy)
- Università degli studi di Milano (Italy)
- Fondazione Istituto Nazionale di Genetica Molecolare (Italy, affiliated)
- University of Zurich (Switzerland, associated)
- University Hospital Vall D'Hebron, Barcelona (Spain)
- University of Münster (Germany)
- University of Verona (Italy)
- The European Multiple Sclerosis Platform (Belgium)