Rebound post-natalizumab may be in response to EBV infected B-cells and plasma cells in the brains of people with MS. I am convinced EBV is the cause of MS and may be stereotypical relapses.
Dr G. I sent you a donation recently but I'm still not subscribed. You must not have gotten it. Anyway, very complex blog. I'll just mention that ata188,in trials now, will kill the ebv laced cells. So are btk inhibitors even worth doing since they will be unable to kill off these ebv laced cells? I mean what's the use of the upcoming btki's. Also, SD we get tested for ebv levels? ( My one neuro denied my request)
Interested in your case study relating to possible relapses when no new symptoms observed but recurrent symptoms without the incidence of concurrent infection. I have been on natalizumab for four and a half years now after a switch from Gilenya and a subsequent relapse experienced shortly after withdrawal. Since that relapse back early 2017 and Natalizumab treatment started almost a year later I have had numerous exacerbations of symptoms similar to the original relapse. These have been related to difficulty using my left leg/knee and continue till this very day. The length and severity of symptoms also vary and gradually are reducing my mobility over time, with the prospect of a significant decrease to come. I thought that the term flare might be a good description for these events as they may be due to a variety of triggers or even no obvious stimulus at all. Again this has not been considered as a relapse at any particular time due to lack of obvious infection and stable MRI's since 2017. Surely these should be considered to be significant in the status of my MS over time and worthy of some attention?
I can't speak to same site relapses but I certainly get symptoms/indicators (not sure what to call them) in the same places. If I am not careful I can bring them on and after 28y I am well aware of what they are and what I have done to achieve them. I get positional sensations if I am static for a while or if I do certain things like clench my toes. Easily avoided/remedied but always there reminders that I have MS.
Many thanks Prof G for your post, just a couple of random questions if you have time..
Do you expect to get similar patterns of EBV in the CNS of healthy individuals, and patterns of EBV reactivating in healthy individuals (corresponding to relapse patterns of those with MS)? Could some of the existing antivirals/spironolactone be used to lessen the viral load in relapses, and lessen relapse severity, I guess this has already been studied?
I have read that the chance of natalizumab rebound decreases with increased treatment time, do you know why, just interested, in some ways I would have expected the opposite?
Given the fact that people keep 'invisibly'progressing on it, is it best to switch from Tysabri even if 'stable'? What about the risks of rebound? Can they be prevented? And what is best to switch to? Are the new BTK drugs likely to be a good option in your opinion, assuming they will be available before any anti-EBV drug is?
Dr G. I sent you a donation recently but I'm still not subscribed. You must not have gotten it. Anyway, very complex blog. I'll just mention that ata188,in trials now, will kill the ebv laced cells. So are btk inhibitors even worth doing since they will be unable to kill off these ebv laced cells? I mean what's the use of the upcoming btki's. Also, SD we get tested for ebv levels? ( My one neuro denied my request)
Rob r.
Interested in your case study relating to possible relapses when no new symptoms observed but recurrent symptoms without the incidence of concurrent infection. I have been on natalizumab for four and a half years now after a switch from Gilenya and a subsequent relapse experienced shortly after withdrawal. Since that relapse back early 2017 and Natalizumab treatment started almost a year later I have had numerous exacerbations of symptoms similar to the original relapse. These have been related to difficulty using my left leg/knee and continue till this very day. The length and severity of symptoms also vary and gradually are reducing my mobility over time, with the prospect of a significant decrease to come. I thought that the term flare might be a good description for these events as they may be due to a variety of triggers or even no obvious stimulus at all. Again this has not been considered as a relapse at any particular time due to lack of obvious infection and stable MRI's since 2017. Surely these should be considered to be significant in the status of my MS over time and worthy of some attention?
I can't speak to same site relapses but I certainly get symptoms/indicators (not sure what to call them) in the same places. If I am not careful I can bring them on and after 28y I am well aware of what they are and what I have done to achieve them. I get positional sensations if I am static for a while or if I do certain things like clench my toes. Easily avoided/remedied but always there reminders that I have MS.
Many thanks Prof G for your post, just a couple of random questions if you have time..
Do you expect to get similar patterns of EBV in the CNS of healthy individuals, and patterns of EBV reactivating in healthy individuals (corresponding to relapse patterns of those with MS)? Could some of the existing antivirals/spironolactone be used to lessen the viral load in relapses, and lessen relapse severity, I guess this has already been studied?
I have read that the chance of natalizumab rebound decreases with increased treatment time, do you know why, just interested, in some ways I would have expected the opposite?
Given the fact that people keep 'invisibly'progressing on it, is it best to switch from Tysabri even if 'stable'? What about the risks of rebound? Can they be prevented? And what is best to switch to? Are the new BTK drugs likely to be a good option in your opinion, assuming they will be available before any anti-EBV drug is?
This makes me extremely nervous about being on Tysabri!
It's only been 7 infusions so far and no new symptoms but wondering if I should now jump ship as they say to Mavenclad..
I do have active disease (2 active spinal lesions) hence the thinking of starting Tysabri first.
The switching off Tysabri makes me equally nervous
I was wondering the other day, how does the EBV hypothesis square with this?
https://www.cell.com/cell/fulltext/S0092-8674(18)31560-5