This year’s ECTRIMS 2024 meeting, from the 18th to the 20th September, in Copenhagen should have something for everyone.
I am told there will be a formal presentation on the new MS diagnostic criteria. Then there is the big reveal with the headline results of the phase 3 Tolebrutinib relapsing and non-relapsing secondary progressive trials. Will they be positive, and if yes, by what margin? As you are aware, Tolebrutinib, a second-generation BTKi, is following on in the gloomy shadow of evobrutinib, which was shown not to be more effective than teriflunomide. There are reasons to be optimistic and pessimistic regarding Tolebrutinib as a treatment for MS. Is anyone prepared to estimate the headline results? I could set up a super-forecasting competition similar to the one I set up a few years ago for ofatumumab. The trial to watch is the non-relapsing secondary progressive or HERCULES trial; this has been designed to see the effect of BTKi on smouldering MS pathology. The billion-dollar question: will it work?
We will also hear about the MS-STAT2 trial, i.e., the impact of high-dose simvastatin on SPMS. If this trial is positive, it will be essential to find out if it will be positive because of the effect of simvastatin on MS pathology or its impact on metabolic health and comorbidities. I am not expecting this trial to be positive. However, if it is positive, I suspect the treatment effect will be marginal in the sense that it could be one step on the ladder to supporting the marginal gains philosophy of treating MS.
What excites me is the immunological data on the role of EBV in the pathogenesis of MS. The more data that supports the role of ongoing EBV infections as a driver of MS disease activity, the more likely we are to get big pharma engaged in testing EBV-targeted antivirals and immunotherapies in MS.
We are taking MS-Selfie to ECTRIMS and presenting an E-Poster on using our DMT InfoCards in MS clinical practice. If you are a healthcare professional, I would like to know if you have used the cards or want to use them in clinical practice. Your feedback will be included as part of our presentation at ECTRIMS.
MS-Selfie will also be present at the ECTRIMS Patient Community Day a dedicated event designed for people with MS. You can attend online and watch remotely. You will need to register via the ECTRIMS 2024 website.
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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 believe the Tolebrutinib BTK trial will also be a flop against SPMS, even though I hope I’m wrong. My rough theory is that we have learned how to target the immune system pretty well- and this repurposing of an existing class of drugs is more an attempt to make easy money for those companies. I have not seen any articles that indicate this method of attack really goes after a main driver ( maybe EBV, maybe something else), so it’s almost a spray and pray attack. Color me a pessimist on your survey, lol. Simvastatin I am not sure about, but my limited understanding is that it does not target anything MS related. If it is just a general improvement type of program, it is no different than the diets that are promoted out there. Again, hope I’m wrong- but not holding out lots of hope.
This might be of some interest. This is not the only study I've read, indicating if you inhibit NF-κB, you can induce apoptosis in EBV infected B-cells.
The effects of inhibiting NF-κB might also be further reaching than just EBV annihilation.
Kind of skeptical on statins but they are cheap enough to go for it even if the effect is relatively small.
But I agree, it would help to know if it only helps in people who would benefit from statins otherwise (my lipids sure don't suggest to get them otherwise).
I have been studying this for the past 18 years, and I found an interesting article that I lost when my computer crashed about 7 years ago, but unfortunately I haven't been able to find it ever since. It had to do with mitochondrial dysfunction being instrumental in MS pathology.
I am not a doctor, nor a professor, so this may seem like a ridiculous mess. But anyway...
Could multiple sclerosis be possibly caused by DRESS as well as EBV, as it can be confused with mono? And DRESS is also known to cause delayed autoimmune diseases.
I too am holding out hope, but not sure of yet another DMT. Re Simvastatin v other statins, I will go back to the archives. Is it supposed to have an anti inflammatory effect? I’ve been on lovastatin for years, heaven knows why, and I will ask my (relatively useless) neuro to change it up. That with Valtex would be my bag of tricks at this point. Good luck, Professor. Stay safe!
Obviously I pray to the g-ds that either the BTK or Sim works. With respect to EBV, Prof. G, how do you respond to the argument that people with no EBV get MS?
Thank you, as always, for your reply and contributions. I did see your video (some time back) and recall that 100% have ebv and those neg were later found to be ebv+ via more sensitive assays. I guess some folks continue to be skeptical of ebv/ms causality but not me. I am pursuaded by the epidemiology.
I believe the Tolebrutinib BTK trial will also be a flop against SPMS, even though I hope I’m wrong. My rough theory is that we have learned how to target the immune system pretty well- and this repurposing of an existing class of drugs is more an attempt to make easy money for those companies. I have not seen any articles that indicate this method of attack really goes after a main driver ( maybe EBV, maybe something else), so it’s almost a spray and pray attack. Color me a pessimist on your survey, lol. Simvastatin I am not sure about, but my limited understanding is that it does not target anything MS related. If it is just a general improvement type of program, it is no different than the diets that are promoted out there. Again, hope I’m wrong- but not holding out lots of hope.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362042/
This might be of some interest. This is not the only study I've read, indicating if you inhibit NF-κB, you can induce apoptosis in EBV infected B-cells.
The effects of inhibiting NF-κB might also be further reaching than just EBV annihilation.
Here's another study looking at how EBV hijacks the mevalonate pathway.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008030
Interesting papers! Thanks for the links.
Yep..
Kind of skeptical on statins but they are cheap enough to go for it even if the effect is relatively small.
But I agree, it would help to know if it only helps in people who would benefit from statins otherwise (my lipids sure don't suggest to get them otherwise).
Not holding my breath on the BTKi, either...
I have been studying this for the past 18 years, and I found an interesting article that I lost when my computer crashed about 7 years ago, but unfortunately I haven't been able to find it ever since. It had to do with mitochondrial dysfunction being instrumental in MS pathology.
I am not a doctor, nor a professor, so this may seem like a ridiculous mess. But anyway...
Could multiple sclerosis be possibly caused by DRESS as well as EBV, as it can be confused with mono? And DRESS is also known to cause delayed autoimmune diseases.
I too am holding out hope, but not sure of yet another DMT. Re Simvastatin v other statins, I will go back to the archives. Is it supposed to have an anti inflammatory effect? I’ve been on lovastatin for years, heaven knows why, and I will ask my (relatively useless) neuro to change it up. That with Valtex would be my bag of tricks at this point. Good luck, Professor. Stay safe!
Obviously I pray to the g-ds that either the BTK or Sim works. With respect to EBV, Prof. G, how do you respond to the argument that people with no EBV get MS?
In our hands 100% of people with MS are EBV positive. Did you watch my talk on MS prevention?
Thank you, as always, for your reply and contributions. I did see your video (some time back) and recall that 100% have ebv and those neg were later found to be ebv+ via more sensitive assays. I guess some folks continue to be skeptical of ebv/ms causality but not me. I am pursuaded by the epidemiology.