For me its a combination of poor science, mode of action and trial design. In addition to what you propose EBV antibody titres should be checked (optimally serum and CSF), I hope we get to see that.
This is despite being unsurprised due to Attara not having enough data points last year (I think) prompting a delay in reporting results.
A recent pre-clinical trial claims not EBV but other Herpes virus contributes. Maybe both? At this point, I am hoping for positive reporting for BTK Inhibitors or Foralumab, despite the latter being some time off. We simply don't have time. I want to scream.
I feel like this is it for a while on any ebv trials for MS unfortunately
Such a shame as this could’ve been so meaningful to our community. Looking at it from a big Pharma lens they would be extremely hesitant to take anything going forward with EBV + MS looking at this so unless we can do a trial that will guarantee a result I don’t see this moving forward
We still have ebv vaccine, car T cell therapies. But this sucks so much as I do believe ebv is the trigger for MS and other diseases.
Why isn't more study being done on already-existing drugs that are known to work against EBV and have been seen anecdotally to have strong therapeutic effects in MS? E.g., TAF, Combivir, etc.
I suspect that it really throws cold water on the EBV hypothesis. If I remember correctly, even the big study that “proved” EBV was the trigger had 1 person who had MS but no sign of EBV; sorta glossed over, but still. I do know a number of MS’ers on various groups who say they have tested negative for EBV, so the link seems tenuous, at best. Too bad that this one didn’t work, and prove me wrong; at 66, I probably won’t ever see the answer. I have a really unscientific hunch that MS is triggered by several things causing several different reactions that all wind up attacking the nervous system, but no proof of that hunch. So cast aspersions, but it presents so differently and responds so differently to people that I think we just have not defined what it is well enough.
OK great but as I recall, the patients from the phase 1 study over a decade ago didn't start to show any response for quite some time. Is ATA188 the treatment that was trialled and failed (it doesn't do much over a short period of time) but over a much longer period patients started to recover function? So they went to phase 2.
Why would anyone expect patients with progressive MS to suddenly start improving if the neurodegeneration stops? You're a neurologist. Do you see stroke patients make sudden recoveries years after their stroke? Or is it more gradual after the initial inflammation settles? With MS - in order for the brain to start repairing itself the attacking "party" must be removed but then there needs to be time for things to settle down and start rewiring. Unless patients were also given some form of stem cell transplant or remyelinating therapy that just isn't going to happen in this timescale.
Bet you a tenner that in 2028 when the data is reviewed suddenly the patients in the treatment arm start to show a remarkable recovery in EDSS from their previous levels... and we go back round the merry-go-round again (hopefully this time with a more sensible trial design!)
This is extremely disappointing. I follow a US woman on Threads and she was a participant in this trial. I was so encouraged by her results. She went from a wheelchair to walking very well, and her fatigue was dramatically reduced. Perhaps she was an anomaly.
As others say, those of us with advanced MS don't have the luxury of time on our side.
I would like to see more trials of anti virals in the meantime, especially as frequent Covid infections are likely to reactivate EBV and Herpes viruses, triggering more MS activity.
Many thanks for the update Prof G, that's really disappointing.
On a different topic; do you know if anyone is looking at drug repurposing for MS using generative AI, I was listening to a podcast about Every Cure and it's use in Castleman disease and rare diseases. Do you have a view on it's potential in MS, I haven't read anything about it's use in the current trials like Octopus etc.
I hate to sound “dense” in all of this, but there is a control group, and more there improved than expected. Since we are looking to stop MS and not necessarily improve it, that gives me pause to begin with. Not getting worse would have been good? But 16% of placebo group improved vs. an expected 4%, or something like that (which I don’t follow- that’s me)? I do know that if you take people who believe something is going to happen and who are highly motivated to believe it and see it come true, some of them will almost always end up believing it did happen. They will walk faster and stumble less. Being treated with the experimental drug, they may change other things like eat better, exercise more, push themselves farther. The controls on this type of work need to be so very good. Was it double blinded by people sworn to “super double secret” secrecy? Something seems to have went askew. God bless all the participants and watchers. Hope something useful can be made of it.
Sorry for being off topic but I’m not sure how else to ask you Prof G. What are your thoughts on taurine and its potential to trigger remyelination? Is it worth taking the supplement or are there risks?
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For me its a combination of poor science, mode of action and trial design. In addition to what you propose EBV antibody titres should be checked (optimally serum and CSF), I hope we get to see that.
Oh wow, i can't believe it (!) :(
I guess curing ms just got postponed for another 50 years because no one will touch it now.
This breaks my heart and add it to the heap.
This is despite being unsurprised due to Attara not having enough data points last year (I think) prompting a delay in reporting results.
A recent pre-clinical trial claims not EBV but other Herpes virus contributes. Maybe both? At this point, I am hoping for positive reporting for BTK Inhibitors or Foralumab, despite the latter being some time off. We simply don't have time. I want to scream.
I feel like this is it for a while on any ebv trials for MS unfortunately
Such a shame as this could’ve been so meaningful to our community. Looking at it from a big Pharma lens they would be extremely hesitant to take anything going forward with EBV + MS looking at this so unless we can do a trial that will guarantee a result I don’t see this moving forward
We still have ebv vaccine, car T cell therapies. But this sucks so much as I do believe ebv is the trigger for MS and other diseases.
It shows how far the leap is from knowing that EBV plays 'a' role to knowing 'what role exactly'.
Why isn't more study being done on already-existing drugs that are known to work against EBV and have been seen anecdotally to have strong therapeutic effects in MS? E.g., TAF, Combivir, etc.
I suspect that it really throws cold water on the EBV hypothesis. If I remember correctly, even the big study that “proved” EBV was the trigger had 1 person who had MS but no sign of EBV; sorta glossed over, but still. I do know a number of MS’ers on various groups who say they have tested negative for EBV, so the link seems tenuous, at best. Too bad that this one didn’t work, and prove me wrong; at 66, I probably won’t ever see the answer. I have a really unscientific hunch that MS is triggered by several things causing several different reactions that all wind up attacking the nervous system, but no proof of that hunch. So cast aspersions, but it presents so differently and responds so differently to people that I think we just have not defined what it is well enough.
OK great but as I recall, the patients from the phase 1 study over a decade ago didn't start to show any response for quite some time. Is ATA188 the treatment that was trialled and failed (it doesn't do much over a short period of time) but over a much longer period patients started to recover function? So they went to phase 2.
Why would anyone expect patients with progressive MS to suddenly start improving if the neurodegeneration stops? You're a neurologist. Do you see stroke patients make sudden recoveries years after their stroke? Or is it more gradual after the initial inflammation settles? With MS - in order for the brain to start repairing itself the attacking "party" must be removed but then there needs to be time for things to settle down and start rewiring. Unless patients were also given some form of stem cell transplant or remyelinating therapy that just isn't going to happen in this timescale.
Bet you a tenner that in 2028 when the data is reviewed suddenly the patients in the treatment arm start to show a remarkable recovery in EDSS from their previous levels... and we go back round the merry-go-round again (hopefully this time with a more sensible trial design!)
This is extremely disappointing. I follow a US woman on Threads and she was a participant in this trial. I was so encouraged by her results. She went from a wheelchair to walking very well, and her fatigue was dramatically reduced. Perhaps she was an anomaly.
As others say, those of us with advanced MS don't have the luxury of time on our side.
I would like to see more trials of anti virals in the meantime, especially as frequent Covid infections are likely to reactivate EBV and Herpes viruses, triggering more MS activity.
Sigh........
I was just reading your LinkedIn post when this arrived in my inbox, I appreciate the deep dive! This is going to break a lot of hearts
Many thanks for the update Prof G, that's really disappointing.
On a different topic; do you know if anyone is looking at drug repurposing for MS using generative AI, I was listening to a podcast about Every Cure and it's use in Castleman disease and rare diseases. Do you have a view on it's potential in MS, I haven't read anything about it's use in the current trials like Octopus etc.
The discussion about EBV “hiding” had me wondering whether there are studies on correlation between Hepatitis B and MS?
Another one bites the dust.
Any chance we will see a trial of the autologous version? That always sounded more likely to be working anyhow
I hate to sound “dense” in all of this, but there is a control group, and more there improved than expected. Since we are looking to stop MS and not necessarily improve it, that gives me pause to begin with. Not getting worse would have been good? But 16% of placebo group improved vs. an expected 4%, or something like that (which I don’t follow- that’s me)? I do know that if you take people who believe something is going to happen and who are highly motivated to believe it and see it come true, some of them will almost always end up believing it did happen. They will walk faster and stumble less. Being treated with the experimental drug, they may change other things like eat better, exercise more, push themselves farther. The controls on this type of work need to be so very good. Was it double blinded by people sworn to “super double secret” secrecy? Something seems to have went askew. God bless all the participants and watchers. Hope something useful can be made of it.
Sorry for being off topic but I’m not sure how else to ask you Prof G. What are your thoughts on taurine and its potential to trigger remyelination? Is it worth taking the supplement or are there risks?