Excellent explanation to start more experiments to zero in on EBV in MS.
ACTRIMS2023 Just concluded and had a strong focus on EBV and MS. Steven Jacobson @NIH presented a slide with Rx contenders for EBV. Don't yet know what he said but in the Antiviral category he listed: Brincidofovir, Raltegravir, Tenofovir, Valacyclovir, Interferons.
Antiretrovirals (TAF, TDF) have published case studies showing multi-year MS NEDA. Followed by cell-assay studies showing TAF most effective (Druso 2020)
But Brincidofovir was the one he put a circle around.
Brincidofovir is a broad antiviral against several DNA viruses, including HHV-6 and EBV for which it has a high EC50 of 10. But would it have any effect on latent EBV or only reactivated?
The antivirals are attractive b/c they are already FDA approved and if effective could help mitigate MS damage, while the vaccines and other therapies go through the long process to approval.
Which antivirals do you think should go into human biomarker trials like you did for Famvir?
Would concurrent animal model testing be helpful? Studies of EBV in a humanized mouse model and rabbit have been published.
You can test anti-EBV in animal models, but it is not going to answer the question of what they will do in MS or not. At the end of the day we need to go ahead and do clinical trials.
Regarding TAF, TDF etc. they may have anti-EBV effects, but they are not optimised to target EBV. We need better more targeted therapies. In addition, the patent life of the antivirals are not sufficient to justify investment in them for a pharma company.
Are there not enough of us from a significant number of countries that we translate this letter and attach it in an open letter to our national ms societies asking them to please print it on their website?
Sure to create some publicity to raise money to do haart?
This is what The Society With MS (SWiMS) is doing. Look them up on Facebook. It’s a worldwide MS research group. They have all the current antiviral trials documented.
Anna Society With MS (SWIMS) is ready to help unite all MS groups to start trials of HAART drugs to target EBV! We are a 501(c)3 non profit, and our members have been donating towards finding a cure for MS. Join the discussion in our FB group and you can help with planning. SammyJo
Sammy I would love to join and spread your message so then we can raise money for trials targeting EBV ! I think pharma companies will be more than happy to see us in action ;-)
Rob, Society With MS (SWIMS) is a 501(c)3 nonprofit, all-volunteer, founded and operated by people with MS determined to speed up trials of curative and regenerative therapies for MS. Our FB group has 3500 members and we're not a support group, rather a research study group. Members discuss the latest medical publications, then I catalog them in our MS Research Database. There are 2 tables, accessed by tabs at the bottom. All Therapies tab has over 100 studies at all phases of research. I modeled it after tables in the medical literature w/ columns for MOA, Modality, Trial Outcomes etc. Our volunteers write detailed profiles on the most promising interventions compiling links to all the research.
The Trial Finder tab has 36 trials in progress, ordered by which will reach Phase 4 the soonest. There are many MS trial lists out there, but I couldn't find any ordered by phase. Our members said this was the most important factor, since many are EDSS>6.5 and age>60 so they don't qualify for trials. So I built it for all my MS friends, as a life planning tool, so we have a realistic outlook on when help will arrive. We may not be scientists, but we do keep up with the science! Have a look here, your suggestions are welcome!
Great ideas! Maybe it is possible to raise money via some official organisation? And spread info among patients who suffer from MS? Or try to organise a campain which will be in social media (facebook/instagram) which can be supported by MS patients around the globe?
Anna. I found this # on linked.in. It is #ebvcausesms. It was made by prof and it has only 10 followers. I think it is because of linked.in., not everyone has it. It is better to create a Group on Facebook titled the same. And then post there this letter translated into different langugages. At the end spread/share this group among others... Its just an idea...
This group already exists. Society With MS (SWiMS) is a 501c3 non profit organization set up to support research. 99% of donations are for MS research. The main focus of SWiMS is finding a cure. EBV is our focus. We are looking at and following the HAART drugs and also looking to help fund those clinical trials, while still keeping an eye on other promising research.
You can start from the ground level or join us in getting more attention towards this cause. We’re always looking for talent to help the cause! We’re 3500 people strong in our FB group and growing!
Anna. You are right! We can translate a letter into different languages and then post it on some kind of groups on Facebook titled "MS is caused by EBV" or another groups where there are MS patients. We can make a kind of "social movement" on the Internet. I know there is similar # on linked.in made by prof G.
Emilia, scroll up to the posts I made about Society With MS, we are a nonprofit and finding a cure for MS is our mission. EBV in MS is our prime focus, and we are just waiting for the word from Prof. G that he has a trial ready for funding! We will unite with all patients and other MS groups who share this goal.
Thank you for your info. But what about also putting some more comments in MS News today profile on Facebook? We can also place some comments in linked.in under # I mentioned. If we place more and more comments everywhere we will spread the idea that "EVB causes MS".
Feb 26, 2023·edited Feb 27, 2023Liked by Gavin Giovannoni
Where can my wife get the tests such as those you mention that can indicate active (and smouldering?) MS please? Should the NHS be doing these as a matter of course if the patient reports worsening symptoms?
Yes, to tests for active MS are based on clinical assessment, MRI and is some cases neurofilament tests.
For smouldering MS the assessment is less defined, but again it includes a clinical assessment, MRI and other imaging markers, patient related outcome measures and dynamic neurological stress tests. Not all HCPs want to find evidence of smouldering disease as we don't have any treatments that work. What we do have is lifestyle manipulation and prevention and treatment of comorbidities.
In the paper: “Roadmap for understanding mechanisms on how Epstein–Barr virus triggers multiple sclerosis and for translating these discoveries in clinical trials.” Steinman et al. The authors say:
“Tenofovir, an antiviral medication used to treat HIV‐1 and chronic hepatitis B, was recently shown to be a potent inhibitor of EBV lytic DNA replication. Tenofovir was listed on clinicaltrials.gov as an add‐on to anti‐CD20 therapies. That trial was withdrawn, but trials are being proposed with Tenofovir and other antivirals in various locations on our planet. It will be important to see whether antiviral activity against both lytic and latent phases of EBV infection will be relevant.”
NB PreP contains tenofovir. Shouldn’t MS patients (like me) just buy PreP online or get it from their GPs as a way of getting an anti-viral quickly while the research (which could take years) takes place?
I think no GP will give us such drug just like that. It can be the fastest way to test if the drug works but all drugs should be first tested in clinical trials, I am afraid :-(
Karen. I am talking about doctors in Poland. I think noone in Poland gives me TAF if it is not tested in clinical trials in MS. Btw - swims are doing good job.
That link is no longer working as the SWiMS group has been dissolved. As the link says, you have to join the Solving MS research study group. There’s a link to it on the page.
This kind of research could really lead to some actual breakthroughs. Thank you for continuing to advocate for it.
As for existing treatments, reading your post, would you agree that teriflunomide is not a bad choiced choice for someone who has recurrent EBV-reactivations, and has been shown to respond to other DMTs (like DMF) with a sharp reduced CD8+ T cell number?
Seems to be very interesting. But as far as I know Octopus cost a lot. I quess such platform focusing on drugs targeting EBV could bring positive and quick response. How was Octopus "invented"? Could we create similar platform only for EBV drugs (but for all types of MS)? Or maybe there is no point cause it cost a lot... And not all from scientific environment will agree to join...
I am afraid we need trials cause we have to prove that drugs work in majority of cases. During the trials health condition, EDSS points, progress of MS are checked. I think we need trials in antivirals because of 3 things- to check once again the theory that EBV causes MS (although I believe we dont have to prove it any more), check if antivirals can help in ms symptoms/Slowing progression and to prove that in order to get rid of ms we need to vaccine our population...
Prof G - I like your post on Linked.in about CD-19 targeted CART-cell therapy. You wrote that there is a chance it can work in MS. At least it works in lupus (it works via anti-EVB mechanism). Do you think such therapy could work in PP MS (or both RR MS and PP MS)? And the beginning of your letter seems like not every pharmaceutical and funding agency would like to focus on anti-EVB drugs in MS... do I understand it correctly? Should we convenience them more ?
The problem with T-cells is that they are very promiscuous and interact with many antigens, but only react (proliferate, make cytokines) to very few antigens. T-cells are the prostitutes of the immunological world. In comparison, antibodies are much monogamous.
I've read about Dr. Michael Levin and his research team from the University of Saskatchewan (USask) College of Medicine - they are looking into the connection between EBV and mutltiple sclerosis (MS) - do you know of any open clinical trials in this in Canada / USA ?
Hello I was taking Tysabri but after contracting meningitis in January I have stopped. I am willing to be a guinea pig for any trials you feel that I would be suitable for. It has been 8 weeks since my last infusion.
You should go on ocrevus asap as Dr G wrote to prevent rebound! Possibly even solumedrol for a bit Rebound can cause more damage and permanent Tell yr neuro!
I think we would need in the order of £6M to do the phase 2a and PoC 2b studies. But the phase 3 programme for registration purposes is in the order of £100M+.
One question. Why ECF Mystery Solved Project has only 127 followers on youtube? It is a great explanation how EBV is connected with MS. Prof G, pls share it in your next post if possible.
Prof. G. shared a registration link (and meeting updates) when they had their conference in early July 2022. SWiMS also shared this. This is coming up: The European Charcot Foundation is holding a Symposium on "Epstein-Barr virus in MS" on March 24 at CONy Congress 2023. If you follow Prof. G. on Twitter, I'm sure he'll post updates.
Excellent explanation to start more experiments to zero in on EBV in MS.
ACTRIMS2023 Just concluded and had a strong focus on EBV and MS. Steven Jacobson @NIH presented a slide with Rx contenders for EBV. Don't yet know what he said but in the Antiviral category he listed: Brincidofovir, Raltegravir, Tenofovir, Valacyclovir, Interferons.
Antiretrovirals (TAF, TDF) have published case studies showing multi-year MS NEDA. Followed by cell-assay studies showing TAF most effective (Druso 2020)
But Brincidofovir was the one he put a circle around.
Slide snapshot: https://twitter.com/drbarrysinger/status/1629178462945820673
Brincidofovir is a broad antiviral against several DNA viruses, including HHV-6 and EBV for which it has a high EC50 of 10. But would it have any effect on latent EBV or only reactivated?
The antivirals are attractive b/c they are already FDA approved and if effective could help mitigate MS damage, while the vaccines and other therapies go through the long process to approval.
Which antivirals do you think should go into human biomarker trials like you did for Famvir?
Would concurrent animal model testing be helpful? Studies of EBV in a humanized mouse model and rabbit have been published.
You can test anti-EBV in animal models, but it is not going to answer the question of what they will do in MS or not. At the end of the day we need to go ahead and do clinical trials.
Regarding TAF, TDF etc. they may have anti-EBV effects, but they are not optimised to target EBV. We need better more targeted therapies. In addition, the patent life of the antivirals are not sufficient to justify investment in them for a pharma company.
Are there not enough of us from a significant number of countries that we translate this letter and attach it in an open letter to our national ms societies asking them to please print it on their website?
Sure to create some publicity to raise money to do haart?
Or am i way off with fhis..
This is what The Society With MS (SWiMS) is doing. Look them up on Facebook. It’s a worldwide MS research group. They have all the current antiviral trials documented.
That's great!
I was thinking about starting *something* which would help fund a HAART study for which i distinctly recall the Prof say 8 or 9 mil dollars.
We could ask swims to ask their followers to draw a butterfly on paper, scan it and upload it with the #haart4ms or similar, why not?
Why not get ALLLLL THE ONGS ON BOARD, EVERYWHERE? This is what I'm saying.
Anna Society With MS (SWIMS) is ready to help unite all MS groups to start trials of HAART drugs to target EBV! We are a 501(c)3 non profit, and our members have been donating towards finding a cure for MS. Join the discussion in our FB group and you can help with planning. SammyJo
Sammy I would love to join and spread your message so then we can raise money for trials targeting EBV ! I think pharma companies will be more than happy to see us in action ;-)
I wouldn't rely on them.theyre a non scientific fb site.
Rob, Society With MS (SWIMS) is a 501(c)3 nonprofit, all-volunteer, founded and operated by people with MS determined to speed up trials of curative and regenerative therapies for MS. Our FB group has 3500 members and we're not a support group, rather a research study group. Members discuss the latest medical publications, then I catalog them in our MS Research Database. There are 2 tables, accessed by tabs at the bottom. All Therapies tab has over 100 studies at all phases of research. I modeled it after tables in the medical literature w/ columns for MOA, Modality, Trial Outcomes etc. Our volunteers write detailed profiles on the most promising interventions compiling links to all the research.
The Trial Finder tab has 36 trials in progress, ordered by which will reach Phase 4 the soonest. There are many MS trial lists out there, but I couldn't find any ordered by phase. Our members said this was the most important factor, since many are EDSS>6.5 and age>60 so they don't qualify for trials. So I built it for all my MS friends, as a life planning tool, so we have a realistic outlook on when help will arrive. We may not be scientists, but we do keep up with the science! Have a look here, your suggestions are welcome!
https://societywithms.org/research-database/
Great ideas! Maybe it is possible to raise money via some official organisation? And spread info among patients who suffer from MS? Or try to organise a campain which will be in social media (facebook/instagram) which can be supported by MS patients around the globe?
So: ok, bu5 we need ideas, no? this is what I'm saying, it needs to get "viral", yes?
Anna. I found this # on linked.in. It is #ebvcausesms. It was made by prof and it has only 10 followers. I think it is because of linked.in., not everyone has it. It is better to create a Group on Facebook titled the same. And then post there this letter translated into different langugages. At the end spread/share this group among others... Its just an idea...
This group already exists. Society With MS (SWiMS) is a 501c3 non profit organization set up to support research. 99% of donations are for MS research. The main focus of SWiMS is finding a cure. EBV is our focus. We are looking at and following the HAART drugs and also looking to help fund those clinical trials, while still keeping an eye on other promising research.
You can start from the ground level or join us in getting more attention towards this cause. We’re always looking for talent to help the cause! We’re 3500 people strong in our FB group and growing!
Anna. You are right! We can translate a letter into different languages and then post it on some kind of groups on Facebook titled "MS is caused by EBV" or another groups where there are MS patients. We can make a kind of "social movement" on the Internet. I know there is similar # on linked.in made by prof G.
Emilia, scroll up to the posts I made about Society With MS, we are a nonprofit and finding a cure for MS is our mission. EBV in MS is our prime focus, and we are just waiting for the word from Prof. G that he has a trial ready for funding! We will unite with all patients and other MS groups who share this goal.
Thank you for your info. But what about also putting some more comments in MS News today profile on Facebook? We can also place some comments in linked.in under # I mentioned. If we place more and more comments everywhere we will spread the idea that "EVB causes MS".
There is a post whether we should target EBV in MS on MS today news on Facebook. Maybe we should express our opinions there? I am adding link: https://m.facebook.com/story.php?story_fbid=pfbid02aBVvzumrdEyiTXXmNKcMJTLjiqQheQmRCcys8dQ5h6yjXA3jMD3azDQTUxLVAbcKl&id=235443516648044
Where can my wife get the tests such as those you mention that can indicate active (and smouldering?) MS please? Should the NHS be doing these as a matter of course if the patient reports worsening symptoms?
Yes, to tests for active MS are based on clinical assessment, MRI and is some cases neurofilament tests.
For smouldering MS the assessment is less defined, but again it includes a clinical assessment, MRI and other imaging markers, patient related outcome measures and dynamic neurological stress tests. Not all HCPs want to find evidence of smouldering disease as we don't have any treatments that work. What we do have is lifestyle manipulation and prevention and treatment of comorbidities.
I would like to be tested for smouldering MS. Prof G, could I get that from my NHS neurologist, and how would you suggest I ask for it, please?
In the paper: “Roadmap for understanding mechanisms on how Epstein–Barr virus triggers multiple sclerosis and for translating these discoveries in clinical trials.” Steinman et al. The authors say:
“Tenofovir, an antiviral medication used to treat HIV‐1 and chronic hepatitis B, was recently shown to be a potent inhibitor of EBV lytic DNA replication. Tenofovir was listed on clinicaltrials.gov as an add‐on to anti‐CD20 therapies. That trial was withdrawn, but trials are being proposed with Tenofovir and other antivirals in various locations on our planet. It will be important to see whether antiviral activity against both lytic and latent phases of EBV infection will be relevant.”
NB PreP contains tenofovir. Shouldn’t MS patients (like me) just buy PreP online or get it from their GPs as a way of getting an anti-viral quickly while the research (which could take years) takes place?
I think no GP will give us such drug just like that. It can be the fastest way to test if the drug works but all drugs should be first tested in clinical trials, I am afraid :-(
Are you only referring to doctors in the UK? I know there are doctors in the US prescribing TDF/TAF off label to MS patients. Many from the SWiMS group are presenting this profile to their doctors for their review: https://docs.google.com/document/d/189uOUWBaXq0nnG2EGJayaQfv88n7lYb2xOp5kbZmK0E/edit?fbclid=IwAR33OEJUnsN4FxEXCYHZXc2KP5rPt4w7U05YCjzjUOCMua0C-fdBzoAiCpE
Of course, this is not to be used as medical advice and one must consult with a healthcare professional.
Karen. I am talking about doctors in Poland. I think noone in Poland gives me TAF if it is not tested in clinical trials in MS. Btw - swims are doing good job.
Sorry to hear that. Thank you! We try to do the best we can to further the EBV/MS link.
Hi, the link is no longer working... Could you be so kind to provide a new link or share the document in any other way? Thanks
That link is no longer working as the SWiMS group has been dissolved. As the link says, you have to join the Solving MS research study group. There’s a link to it on the page.
What is NB PreP?
This kind of research could really lead to some actual breakthroughs. Thank you for continuing to advocate for it.
As for existing treatments, reading your post, would you agree that teriflunomide is not a bad choiced choice for someone who has recurrent EBV-reactivations, and has been shown to respond to other DMTs (like DMF) with a sharp reduced CD8+ T cell number?
Teriflunomide is anti-EBV and should prevent lytic-latent cycling at least in the periphery. It does not penetrate the CNS very well.
Question:
I forgot the name of it (might be octapus trial) - the trial where they throw drugs at ppms and see what sticks.
In essence - why cant we have a study like that for rrms so we can try antivirals?
Or am i losing the plot here?
No you are not losing the plot. Yes, we need a trial platform to test antivirals.
Seems to be very interesting. But as far as I know Octopus cost a lot. I quess such platform focusing on drugs targeting EBV could bring positive and quick response. How was Octopus "invented"? Could we create similar platform only for EBV drugs (but for all types of MS)? Or maybe there is no point cause it cost a lot... And not all from scientific environment will agree to join...
Exactly.. afai can remember octapus is something along the lines of... "we think x,y,z might work so we'll try it".
Does Octapus even allow antivirals? Or was is designed to repurpose generics or something along those lines...
Anyway..So.. why cant we just take one person and give him/her antivirals ? Just one? And go from there?
I am afraid we need trials cause we have to prove that drugs work in majority of cases. During the trials health condition, EDSS points, progress of MS are checked. I think we need trials in antivirals because of 3 things- to check once again the theory that EBV causes MS (although I believe we dont have to prove it any more), check if antivirals can help in ms symptoms/Slowing progression and to prove that in order to get rid of ms we need to vaccine our population...
Ah yeah, the old "antivirals don't work, we need a vaccine" spiel.
Though I can't think where i heard it all before.. :)
Prof G - I like your post on Linked.in about CD-19 targeted CART-cell therapy. You wrote that there is a chance it can work in MS. At least it works in lupus (it works via anti-EVB mechanism). Do you think such therapy could work in PP MS (or both RR MS and PP MS)? And the beginning of your letter seems like not every pharmaceutical and funding agency would like to focus on anti-EVB drugs in MS... do I understand it correctly? Should we convenience them more ?
Yes, investing in MS is risky and expensive and quite complex. This is why many Pharma companies are nervous to do so.
"For fools rush in where angels fear to tread"
In this context, does EBV PCR test done at time of relapse has any significance? It's negative in many cases.
It does not mean anything. The peripheral blood is unlikely where the action is in terms of MS.
Forgot to mention, I meant CSF PCR. Usually done at time of diagnosis.
In my opinion, If there are self antigens outside CNS and there is no autoimmunity, we should investigate why it hapens first. Any thoughts?
The problem with T-cells is that they are very promiscuous and interact with many antigens, but only react (proliferate, make cytokines) to very few antigens. T-cells are the prostitutes of the immunological world. In comparison, antibodies are much monogamous.
I've read about Dr. Michael Levin and his research team from the University of Saskatchewan (USask) College of Medicine - they are looking into the connection between EBV and mutltiple sclerosis (MS) - do you know of any open clinical trials in this in Canada / USA ?
Not that I am aware of.
Trifling concern, but for those of us whose phones are too old to support the Substack app, is there another way to listen to the audio versions?
On the Web via a browser
That used to be the case, but audio has dropped off for the last few posts. It doesn't appear in Firefox or Safari. But as I say, a trifling concern
Hello I was taking Tysabri but after contracting meningitis in January I have stopped. I am willing to be a guinea pig for any trials you feel that I would be suitable for. It has been 8 weeks since my last infusion.
You need to be careful as you are getting close to the window where natalizumab levels will drop and potential rebound.
You should go on ocrevus asap as Dr G wrote to prevent rebound! Possibly even solumedrol for a bit Rebound can cause more damage and permanent Tell yr neuro!
How much do you think these trials would cost? Is it worth looking for some philanthropists rather than pharmaceutical companies or funding agencies?
I think we would need in the order of £6M to do the phase 2a and PoC 2b studies. But the phase 3 programme for registration purposes is in the order of £100M+.
https://www.clinicaltrials.gov/study/NCT05957913 is the link to the US PrEP trial, The patient led US group behind this trial is called Solving MS Their website is https://solvingms.org/
One question. Why ECF Mystery Solved Project has only 127 followers on youtube? It is a great explanation how EBV is connected with MS. Prof G, pls share it in your next post if possible.
Prof. G. shared a registration link (and meeting updates) when they had their conference in early July 2022. SWiMS also shared this. This is coming up: The European Charcot Foundation is holding a Symposium on "Epstein-Barr virus in MS" on March 24 at CONy Congress 2023. If you follow Prof. G. on Twitter, I'm sure he'll post updates.
Thanks for your replay and help :-) i will follow it for sure.
My pleasure:)