NOBEL SYMPOSIUM™ Multiple Sclerosis: Past, Present and Future Treatments
2nd-5th of June 2025 | Jacob Berzelius lecture hall | Stockholm, Sweden
I am privileged to be invited to speak at a Nobel Symposium this week on ‘Multiple Sclerosis: from molecular mechanisms to disease-modifying treatments’. This is an invitation-only meeting and a closed circle of the other half of the scientific world of MS. What do you think of the programme? Do you think they have left anything out? What questions would you like to ask?
The first three days are closed to invited delegates. I will speak on day four, Thursday, 5th June, the open day, which is open to the public and people with MS. The open day is about the treatments of MS and the future. When I was invited to speak, I was given a blank sheet. I have decided to focus on my current research interest in MS prevention and the role of EBV in the pathogenesis of MS. I have entitled my talk ‘Infectious mononucleosis - a pragmatic target for preventing multiple sclerosis’.
On arriving at the symposium, a colleague from Italy said that funding for MS research is drying up because of the impact of biosimilars on the field. He implied that development pipelines are drying up because big pharma does not think there is any money to make out of the future treatment of MS. He implied that the MS community is satisfied that the efficacy of anti-CD20 therapy is sufficient to manage MS. Clearly, I disagreed. What about smouldering MS? I told him we need a CNS penetrant approach to stop smouldering MS.
I then gave him a thought experiment to consider. What will happen to the field of MS if fenebrutinib proves to be a superior therapy to ocrelizumab in primary progressive MS? Will that change the field, i.e., move it from anti-CD20 to focus on CNS mechanisms? He may be satisfied with NEIDA (no evident inflammatory disease activity) as a treatment target. We also have to switch off smouldering MS, and our attention should shift to NESDA (no evident smouldering disease activity) and beyond. Do you agree?
I am getting more bullish about fenebrutinib, and I am now giving fenebrutinib about a 60% (range 40-80%) chance of being superior to ocrelizumab in treating primary progressive MS. This is based on tolebrutinib results in non-relapsing SPMS, fenebrutinib CNS penetration data and its anti-inflammatory effects seen on the phase 2 extension trial and the fact that BTKi are pan anti-EBV drugs targeting latent EBV infection.
Thinking beyond BTKIs, what about CD19-targeted CAR T-cell therapies, EBV antivirals, and EBV immunotherapies? The MS community should take a philosophical approach to its thinking. I would start by defining and getting consensus on defining an MS cure. We can then look for cures, whether spontaneous or secondary to MS treatment. My focus will be on EBV and MS prevention, but then I am biased.
The good thing about meetings like this is the time for thinking and reflection. When I have the time, I will update you and record my talk so you can hear about IM and MS prevention.
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Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
I don’t know about a cure but we haven’t even IEd the antigen in MS. Biomarkers exist, but there’s not one single blood/csf test to nail the diagnosis. As for EBV,
While EBV infection likely contributes to MS risk, the hypothesis that EBV is the singular or primary cause of MS is oversimplified. A more plausible model is that EBV acts as one of many necessary co-factors in genetically susceptible individuals—part of a multifactorial disease process. The causality remains unproven. No EBV directed Rx works.
Axonal loss occurs early. We can talk about oligodendrocytes and microglia and other resident CNS cells but axonal loss is permanent and that is why young patients who end up being in a wheelchair or are completely disabled unfortunately cannot be told that there is a cure around the corner. We have barely scratched or even addressed the neurodegenerative component of MS.
Jay Avasarala
U of KY
You know how to wind me up!
“He implied that the MS community is satisfied that the efficacy of anti-CD20 therapy is sufficient to manage MS.”
What world do these people live in? Channel 4 News last week had a piece on the Octopus trial with a 38 year old PPMSer confined to his flat. The MS Society website includes a story of a 23 year old woman with advanced MS who lives in a care home.
MS academia seem to be in denial about the real disease (neurodegenerative disease) and the failure of current therapies to have any meaningful impact on it.
I wonder if the family and friends of former footballer Tom Youngs are satisfied with the efficacy of anti-CD20 therapy?
https://www.dailymail.co.uk/sport/football/article-14680035/Former-footballer-dies-45-Tom-Youngs.html