MS is primarily a neuro-degenerative disease. As the brain and spinal cord are gradually destroyed, the result is ever increasing disability. EDSS 10 is death from MS. The immune system response is just that - a response to the damage caused by the neuro-degeneration. Yet researchers keep lumping MS with so called auto-immune diseases and are obsessed with taming the immune response not the cause / mechanisms of the neuro-degeneration. Surely there are more similarities with other neuro-degenerative diseases like Parkinson’s, MND or Alzheimer’s and the researchers of these diseases should pool their resources to find ways to stop the neuro-degeneration. Do we really know that much more about MS than was known in Charcot’s time? Maybe it’s just super complicated, or maybe ‘immunology’ (the wretched EAE and too much focus on addressing relapses (not the real disease)) was the wrong specialism to unpick the disease and come up with therapies to tackle neuro-degeneration.
Yes your newsletters are very informative. No one in my MS team really informs me of anything. It’s like they are the holders of the knowledge but very little if it filters down to me. The MS charity websites have very broad based information with no depth.
From your newsletters I now know what questions to ask my neurologist and hos to get more help. how to manage my disease better.
To echo some previous comments, this one is a tad challenging to digest for a layman but the resources are available to decipher most of the information you present.
I always look forward to your posts with enthusiasm, regardless of their complexity, because they provide information that is much more detailed than any other MS specific site and I for one value that immensely. I can safely say I owe 90% of my MS knowledge to your posts, not just for their content but also due to being encouraged to then pursue information on other peer reviewed sites.
I always look through your brilliant articles. Many of them I find enlightening and exciting. I am always aware that on certain occasions I am not equipped or qualified to be entitled to comment. Your article on the immune Tolerance in MS was one such article. Speaking personally, it was like being on a Big Dipper ride with the expectation of good news overcome with disappointment - I suppose that is what medical research is all about.
I have to confess that I found this particular paper very difficult to follow. That is not a criticism - it is more of a confession.
But I remain enormously grateful to you Gavin for the care and consideration you give to the study, research and treatment of MS.
Can frexalimab be also used in ppms? If yes will it be tested in this form as well? And dont you think that ATA188 clinical trial can show us whether ms is an autoimmune disease or not? Thank you Prof for your newsletter. As usually it helps us a lot :-)
Thanks for today's offering. It comes with a steeper learning curve than some and I will re-read several times pausing to look up many references along the way!
Oct 5, 2023·edited Oct 5, 2023Liked by Gavin Giovannoni
Yes, I find your research-related newsletter extremely interesting, if not vital. You examine and evaluate the rationales of the questions driving research, while taking into account the motives of stakeholders.This is critical in order to more objectively understand and assess the current state of MS research. Profit-seeking pharmaceutical companies shouldn't be alone in setting the agenda. Hence, Solving MS was founded this year, to give patients a voice and seat at the table. (Read more at SolvingMS.org about the Harvard MS trial that almost didn't happen this summer until we stepped in.) So these analyses and commentary are most welcome by pwMS, Professor G; thank you and please keep it coming!
It’s so helpful! I’m a STEM researcher, but not in medicine, you highlighting timely studies to be aware of is so useful! That way, those of us non-medics who want to stay current with research can keep tabs on new developments without having to wade through numerous articles that aren’t what we need to know. I’m also always interested in your take on heavily publicised studies like this one, so thank you.
I love the idea of immune tolerance, of "tricking" the immune system to ignore the EBV antigen, which in effect would stop the friendly fire once it hitches a ride on trojan horse T-Cells allowed past the BBB. If we can't kill the virus itself, this may be the best option as it shuts down the entire EBV system.
Somewhat related question... It’s been a year since EBV was confirmed as the trigger for MS. I'd also bet money it's the driver. Knowing that, why are we not testing with simple EBV antigen blood panels to monitor activity? Why are we not using this to monitor viral load when testing new (and old) MS therapies?
This week, I’ve felt horrible and haven’t been able to normalize my inflammation. I had a hunch, so after being denied the EBV panel test by my GP, I went out of pocket and had it done.
I knew I “HAD” EBV because I have MS, and I knew certain markers stayed for life, but they were sky-high. It also showed Anti-VCA IgM within the “equivocal” range, which means ACTIVE, as Anti-VCA IgM appears early in an active EBV infection and usually disappears within four to six weeks.
As of now, I’ve yet to find any long-term studies to compare mine to. What is the normal range for MS, and how much do they fluctuate? And why is this not used as an easy, cost-effective marker, especially if lytic EBV can be detected and coordinates with MS flares? What am I missing?
MS is primarily a neuro-degenerative disease. As the brain and spinal cord are gradually destroyed, the result is ever increasing disability. EDSS 10 is death from MS. The immune system response is just that - a response to the damage caused by the neuro-degeneration. Yet researchers keep lumping MS with so called auto-immune diseases and are obsessed with taming the immune response not the cause / mechanisms of the neuro-degeneration. Surely there are more similarities with other neuro-degenerative diseases like Parkinson’s, MND or Alzheimer’s and the researchers of these diseases should pool their resources to find ways to stop the neuro-degeneration. Do we really know that much more about MS than was known in Charcot’s time? Maybe it’s just super complicated, or maybe ‘immunology’ (the wretched EAE and too much focus on addressing relapses (not the real disease)) was the wrong specialism to unpick the disease and come up with therapies to tackle neuro-degeneration.
Yes your newsletters are very informative. No one in my MS team really informs me of anything. It’s like they are the holders of the knowledge but very little if it filters down to me. The MS charity websites have very broad based information with no depth.
From your newsletters I now know what questions to ask my neurologist and hos to get more help. how to manage my disease better.
Many thanks
Susan
Hi Prof G
To echo some previous comments, this one is a tad challenging to digest for a layman but the resources are available to decipher most of the information you present.
I always look forward to your posts with enthusiasm, regardless of their complexity, because they provide information that is much more detailed than any other MS specific site and I for one value that immensely. I can safely say I owe 90% of my MS knowledge to your posts, not just for their content but also due to being encouraged to then pursue information on other peer reviewed sites.
Please keep them coming.
Regards
Steve
Hi Gavn
I always look through your brilliant articles. Many of them I find enlightening and exciting. I am always aware that on certain occasions I am not equipped or qualified to be entitled to comment. Your article on the immune Tolerance in MS was one such article. Speaking personally, it was like being on a Big Dipper ride with the expectation of good news overcome with disappointment - I suppose that is what medical research is all about.
I have to confess that I found this particular paper very difficult to follow. That is not a criticism - it is more of a confession.
But I remain enormously grateful to you Gavin for the care and consideration you give to the study, research and treatment of MS.
Many thanks for all you do - John
Can frexalimab be also used in ppms? If yes will it be tested in this form as well? And dont you think that ATA188 clinical trial can show us whether ms is an autoimmune disease or not? Thank you Prof for your newsletter. As usually it helps us a lot :-)
Hi,
What does the abbreviation IM stand for?
Susan
Thanks for today's offering. It comes with a steeper learning curve than some and I will re-read several times pausing to look up many references along the way!
Yes, I find your research-related newsletter extremely interesting, if not vital. You examine and evaluate the rationales of the questions driving research, while taking into account the motives of stakeholders.This is critical in order to more objectively understand and assess the current state of MS research. Profit-seeking pharmaceutical companies shouldn't be alone in setting the agenda. Hence, Solving MS was founded this year, to give patients a voice and seat at the table. (Read more at SolvingMS.org about the Harvard MS trial that almost didn't happen this summer until we stepped in.) So these analyses and commentary are most welcome by pwMS, Professor G; thank you and please keep it coming!
Please can you put my name on the long-list for one of the Ph3 Frexalimab trials whenever they come about?
I’d also be interested in Gavin’s response to Ian’s comment below, about immune response to neurodegeneration
It’s so helpful! I’m a STEM researcher, but not in medicine, you highlighting timely studies to be aware of is so useful! That way, those of us non-medics who want to stay current with research can keep tabs on new developments without having to wade through numerous articles that aren’t what we need to know. I’m also always interested in your take on heavily publicised studies like this one, so thank you.
I love the idea of immune tolerance, of "tricking" the immune system to ignore the EBV antigen, which in effect would stop the friendly fire once it hitches a ride on trojan horse T-Cells allowed past the BBB. If we can't kill the virus itself, this may be the best option as it shuts down the entire EBV system.
Somewhat related question... It’s been a year since EBV was confirmed as the trigger for MS. I'd also bet money it's the driver. Knowing that, why are we not testing with simple EBV antigen blood panels to monitor activity? Why are we not using this to monitor viral load when testing new (and old) MS therapies?
This week, I’ve felt horrible and haven’t been able to normalize my inflammation. I had a hunch, so after being denied the EBV panel test by my GP, I went out of pocket and had it done.
https://substack.com/@anajohns/note/c-41776643?utm_source=notes-share-action&r=2sqhq4 <-(test results pic. I couldn't figure out how to attach)
I knew I “HAD” EBV because I have MS, and I knew certain markers stayed for life, but they were sky-high. It also showed Anti-VCA IgM within the “equivocal” range, which means ACTIVE, as Anti-VCA IgM appears early in an active EBV infection and usually disappears within four to six weeks.
As of now, I’ve yet to find any long-term studies to compare mine to. What is the normal range for MS, and how much do they fluctuate? And why is this not used as an easy, cost-effective marker, especially if lytic EBV can be detected and coordinates with MS flares? What am I missing?
https://substack.com/profile/94324668-anna/note/c-41832927?utm_source=notes-share-action&r=1k5pdo