We and others have made the case that certain viruses are important in the pathogenesis of MS. Now I have no problem with this, but how do you show this and what do you do about it?
A case has been made that some MS drugs have anti-viral activity, indeed interferons interfere with viral replication. So drugs deplete the cells where the EBV virus hides/ So is it anti-viral.
But then we have teriflunomide. In the paper the prof-Gs make the case that it is anti-viral. It is anti-proliferative and so should inhibit viral replication as these replicate as the cell divides. However, you can’t have it both ways and if teriflunomide is great at inhibition of EBV and EBV is so important in MS….why isn’t teriflunomide that potent compared to other treatments?
If the anti-viral effect is key, maybe it is not that good as an anti-viral. You can’t have it both ways.
I believe that teriflunomide is not a cure….so what should we expect if we target EBV in MS? We already can see that anti-EBV T cell therapy is not a cure, based on the data presented so far. Is EBV really the important thing to target during MS.
I could easily argue that the effect of EBV has happened a long time before you get diagnosed then it should not do anything. Remember people seem to get infected with EBV long before MS gets diagnosed, so I would argue that targeting EBV in MS is maybe too late. Time will tell
Gold et al. Effect of teriflunomide on Epstein–Barr virus shedding in relapsing-remitting multiple sclerosis patients: Outcomes from a real-world pilot cohort study
Background: Given its potential antiviral activity, we investigated the effect of teriflunomide on EBV in patients with relapsing-remitting MS (RRMS).
Methods:Saliva samples were collected at home and analysed for EBV DNA presence in patients with RRMS treated with teriflunomide for ≥3 months.
Results: : The proportion of patients with detectable EBV in the teriflunomide cohort was lower than in the reference cohorts. The proportion of samples with EBV DNA or shedding from teriflunomide-treated patients was reduced relative to each reference cohort (P<0.0001; >5.8 virus copies/µL cut-off).
Conclusion:This pilot study demonstrated the feasibility of at-home saliva sample collection and revealed a possible effect of teriflunomide on EBV shedding.
coI None
D
A quick google came up w a clinical study (10/1/2022 start date) attempting to address anti-ebv T cell failure in ebv related cancers by administering T cells modified to survive longer in the body. I doubt their approach will be wo significant side effects (cytokine storm alerts going off in my layman’s mind) but the goal of improving saturation of “live” T cells might be exactly what is needed to achieve the desired outcome. I don’t think one can toss out EBV as a target for very strong, effective disease management based on results in relatively early/prototype-development T cell therapy studies. I don’t recall y’all making such jumps with anti-cd20. Such a strange post…was it meant to be a conversation stimulant?
I’m not tossing anything out but asking a simple.question….as for cd20 it does deplete B cells which are the hiding place for EBV.. however I have not said this is why it works.
I thought Aubagio was as effective as anti-CD20 therapy on brain volume loss? So isn’t it as potent as the anti-CD20 therapies?
Yes indeed but is that as good as anti CD20 or as bad as antiCD20 but it should be the best of the best
and for those 2 years
P<0.0001
Dose this make a diference
Those
ok, teriflunomide reduce EB so whats next?
EBV is not needed for constant progression, but it is needed as a trigger. And that trigger can be pulled repeatedly over a very long time.
In other words: EBV is triggering MS and doing _something_ to the B-cells (https://www.msard-journal.com/article/S2211-0348(17)30118-9/fulltext). Eventually, autoimmunity starts as a result, even without EBV being present in B-cells.
Eliminating EBV won’t stop the cascade already in place, so these therapies will only stop the trigger-pulling, but won’t help immediately. Not as long as compromised (and yet EBV-free) B-cells are causing havoc.
That’s why anti-B-cell therapies work better. They stop the B-cells directly and break the cycle in two ways: They are removing faulty B-cells AND as a side effect of removing B-cells are also eliminating EBV (at the very least partly).
The best approach would be to first clear B-cells with Ocrelizumab (maybe 2-3 cycles, or one-time higher dosed to get all of them, even in poorly circulated tissues) followed by a potent EBV-antiviral right after the first dose.
Why this isn’t done already is beyond me.
I has been done by ProfK…when he was using off label cladribine…safety was the name of the game and in addition to storage of sex cells….people were also given an anti-viral (famciclovir) that treats herpes viruses to protect against depletion associated infection but it has some EBV activity.