An induction-maintenance trial with glofitamab (antiCD20/CD3) in MS; induction to purge EBV from the peripheral compartment and a maintenance phase with a safe and well-tolerated EBV antiviral.
pwMS here, n the us, and mild disability (and would like to keep it that way!) and lots of experience professionally with pharma companies. I don't want to incur more damage. Once the brain and spine are damaged it's too late.
If allowed to progress MS may not be "fatal" but it effectively can ruin a life. Hit it hard and hit it early!
Thank you so much for what you do. And for sharing with us. I am planning on heading to Mexico next year for hsct. The last treatment I had was Lemtrada back in 2016. I have continued to relapse, although this is not evidenced via mri. Because of the lack of mri evidence my neuro team are not willing to put me onto another treatment. Hence Mexico. I am aware that some people are considered ‘non-responders’ to hsct, and have been excitedly focused by your work around the EBV for this reason. Incase I am myself a non-responder.
I experienced glandular fever 31 years ago and have been diagnosed with rrms for 21 years this year. Your work on EBV is giving me so much hope!
Sam, That sounds like a rough deal to me. I wish you everything of best.
I am looking into something similar too. I want to join a trial to help move treatment on, but can't afford to not get hsct in the trial and have to do it later anyway.
Was diagnosed with pars planitis at 13. Before anyone realised it would be the start of my Ms and Adhd journey. Feels like I have been on the receiving end of Ms and masty side effects of DMD etc. This feels like for once I will be able to play attack, rather than continuing with defence that I have for almost 30 years. 🥷
I echo your words about Prof Giavannoni and the Ms Selfie Community as a whole. 🙏
Thank you for this post. Just spent a very enlightening hour or so reading around CAR T cells! Sound to be hugely exciting in cancer field but not without risk as you say.
Question: are Atara's T cell immunotherapies ATA188 (allogeneic) and ATA190 (autologous) CAR-T cells? Sound like it, but term doesn't seem to be used?
Dual binding domain antibodies sound to be a nice solution linking T cell to B cells. So (to my mind)) like constructing the bound CAR-T cell in situ.
Unrelated question: have often wondered whether hydroxychloroquine might work (at least in part) as an antiviral in SLE and MS? Definitely gets into the brain 🙂
All exciting stuff. Yes, there is preliminary data that hydroxychloroquine works in MS and it is antiviral. The question is will enough get into the CNS and at high enough concentrations to impact EBV. I will a do a separate post on hydroxychloroquine to discuss its mode of action and potential as a MS DMT.
Re: Question: are Atara's T cell immunotherapies ATA188 (allogeneic) and ATA190 (autologous) CAR-T cells?
These are not CAR T-cells. They are however EBV reactive and selected and grown-up in the lab in response to EBV proteins. In comparison CAR T-cells are genetically engineered.
I agree it should be up to the patient how much risk they take. I moved to London to have Lemtrada at Royal London (I couldn't get it where I'm from); compared to everything else I've been through Lemtrada wasn't a big deal. I'd have had AHSCT if I'd fit the criteria. (I was on Famciclovir after Lemtrada; I didn't notice any effects, other than nausea.)
For me personally, I just want to feel better and undo some of the damage MS has done to me; I'd try any treatment that might do that. I know nothing about EBV, but I'd be in trials for anything that might help me 🤷
A rather severe quotation, which I am sure you will approve. Karl Popper. Whenever a theory appears to you as the only possible one, take this as a sign that you have neither understood the theory nor the problem which it was intended to solve' A Sherlock Holmes opined, 'These are deep waters Watson'. They were.
I can't comment on the scientific part of the post - I don't have the necessary knowledge (yet). But I'm thinking more and more about enlisting the help of a medical student to explain some of the concepts that always appear in MS articles :).
My comment is dedicated to the "killjoys" I encountered quite a few on my way to aHSCT. The thing that I found outrageous was the paternalistic approach that these types of doctors have towards us. Multiple sclerosis is a disease that impacts people differently depending on their age, their experiences, the course of the disease, metaphysical views (is staying alive at all costs an ultimate goal?) etc. Therefore, the boundaries of what we can accept or tolerate, in this world of MS filled with uncertainties, differ from person to person.
This is why I found the mantra that was repeated to me as the reason for refusing aHSCT (and I had active lesions after first line treatment) - "people don't die from DMT, HSCT is more dangerous" - unacceptable. First of all these doctors never gave me the opportunity to present my arguments on the "danger" (exaggerated because based on old data) of HSCT, nor on the fact that MS treatment goes beyond the control of active lesions visible on MRI. I was just told - "you don't need that".
My point is that today we refuse to administer a drug or launch a search for therapeutic solutions based on the notion of "danger" or "benefit-risk balance", not that of patients who know their limits of acceptability, but that of doctors who do not live with the disease on a daily basis and who do not necessarily have the same limits. One day I came across a comment saying "if a promising MS treatement carried a 20% risk of death, I would still be willing to try it because there are things I fear much more than death". 20% may be too much :) but this statement illustrates my point.
There are many MS patients who are willing to take the risk, as in the case of T-CAR for instance, the risk is not blind but after an explanation by professionals. But the killjoys refuse us this choice just because "you don't need it".
I wanted to say that I don't agree with the Killjoys. They have not walked a mile in our shoes. How can they ever get the daily., hourly, minute or seconds that Ms impacts on.
"These killjoys tend to be the same people who don’t agree with using AHSCT and alemtuzumab as a treatment for MS. Do you agree with them?"
I had mono 3 years ago at the age of 33. After 2 years I noticed first symptoms of MS. Usually it takes 7-8 years till the virus triggers MS. Is it possible that EVB starts to be "active" and drives MS so fast?
"what about crazy immunosuppressive anti-cancer therapies as anti-virals?"
What about anti-virals as anti-virals?
There seems to be a vanishingly small number of HIV patients on anti-retrovirals who have any kind of active MS.
There are plenty of anecdotal reports of patients on Tenofovir Alafenamide Fumarate (TAF, Vemlidy) not just NEDA but no PIRA (no progression / smouldering).
I'm trying to persuade my neurologist to let me try TAF. The other option (get myself infected with HIV or Hepatitis-B to force the decision) doesn't seem like a wise choice but desperate times necessitate desperate measures and time is brain etc.
Your first diagram is spot on and how there are the multiple factors in multiple sclerosis. The factors, in my opinion, are Genetics, Environment and EBV.
You can reach out to me and I can give you specific details around my family situation with this triangle of factors.
What about someone with "naturally" low CD19 count in blood (in absence of previous DMD)? Would antiCD19 Abs still work or is CNS targetting agent better (only) option?
This is fascinating. I don’t think you are off the mark or single minded. At my age, new or more aggressive treatments aren’t an option, but herpes breakouts are constant - shingles, HSVs. I recall having mono as a child, perhaps 12? I never thought a thing about it until I became tired in my early 30s. I’m taking Valtrex now on a regular basis. A vaccine or a cure for EBV would be a truly amazing thing, particularly given your research with pw/MS. I’ve thought that if we have the zoster and HPV vaccines, how about some other HV vaccines? Thank you for your support and hard work for us. Please take care of yourself! (Delegate!) :)
Few questions - 1. could both theories of how EBV influences MS be true; 2. What cells EBV is infecting in CNS; 3. Aren't T-cells response increased for most when one is on Natalizumab?
I would love to help if I can.
pwMS here, n the us, and mild disability (and would like to keep it that way!) and lots of experience professionally with pharma companies. I don't want to incur more damage. Once the brain and spine are damaged it's too late.
If allowed to progress MS may not be "fatal" but it effectively can ruin a life. Hit it hard and hit it early!
Thank you for all your hard work and sharing your research via this page.
Are there any clinical trials we can be a part of yet with regards to anti-virals/ EBV and MS. Or any developments in combining this data with DMT?
Best wishes
Fatma
Thank you so much for what you do. And for sharing with us. I am planning on heading to Mexico next year for hsct. The last treatment I had was Lemtrada back in 2016. I have continued to relapse, although this is not evidenced via mri. Because of the lack of mri evidence my neuro team are not willing to put me onto another treatment. Hence Mexico. I am aware that some people are considered ‘non-responders’ to hsct, and have been excitedly focused by your work around the EBV for this reason. Incase I am myself a non-responder.
I experienced glandular fever 31 years ago and have been diagnosed with rrms for 21 years this year. Your work on EBV is giving me so much hope!
Sam, That sounds like a rough deal to me. I wish you everything of best.
I am looking into something similar too. I want to join a trial to help move treatment on, but can't afford to not get hsct in the trial and have to do it later anyway.
Was diagnosed with pars planitis at 13. Before anyone realised it would be the start of my Ms and Adhd journey. Feels like I have been on the receiving end of Ms and masty side effects of DMD etc. This feels like for once I will be able to play attack, rather than continuing with defence that I have for almost 30 years. 🥷
I echo your words about Prof Giavannoni and the Ms Selfie Community as a whole. 🙏
Thank you for this post. Just spent a very enlightening hour or so reading around CAR T cells! Sound to be hugely exciting in cancer field but not without risk as you say.
Question: are Atara's T cell immunotherapies ATA188 (allogeneic) and ATA190 (autologous) CAR-T cells? Sound like it, but term doesn't seem to be used?
Dual binding domain antibodies sound to be a nice solution linking T cell to B cells. So (to my mind)) like constructing the bound CAR-T cell in situ.
Unrelated question: have often wondered whether hydroxychloroquine might work (at least in part) as an antiviral in SLE and MS? Definitely gets into the brain 🙂
All exciting stuff. Yes, there is preliminary data that hydroxychloroquine works in MS and it is antiviral. The question is will enough get into the CNS and at high enough concentrations to impact EBV. I will a do a separate post on hydroxychloroquine to discuss its mode of action and potential as a MS DMT.
Re: Question: are Atara's T cell immunotherapies ATA188 (allogeneic) and ATA190 (autologous) CAR-T cells?
These are not CAR T-cells. They are however EBV reactive and selected and grown-up in the lab in response to EBV proteins. In comparison CAR T-cells are genetically engineered.
I agree it should be up to the patient how much risk they take. I moved to London to have Lemtrada at Royal London (I couldn't get it where I'm from); compared to everything else I've been through Lemtrada wasn't a big deal. I'd have had AHSCT if I'd fit the criteria. (I was on Famciclovir after Lemtrada; I didn't notice any effects, other than nausea.)
For me personally, I just want to feel better and undo some of the damage MS has done to me; I'd try any treatment that might do that. I know nothing about EBV, but I'd be in trials for anything that might help me 🤷
A rather severe quotation, which I am sure you will approve. Karl Popper. Whenever a theory appears to you as the only possible one, take this as a sign that you have neither understood the theory nor the problem which it was intended to solve' A Sherlock Holmes opined, 'These are deep waters Watson'. They were.
I can't comment on the scientific part of the post - I don't have the necessary knowledge (yet). But I'm thinking more and more about enlisting the help of a medical student to explain some of the concepts that always appear in MS articles :).
My comment is dedicated to the "killjoys" I encountered quite a few on my way to aHSCT. The thing that I found outrageous was the paternalistic approach that these types of doctors have towards us. Multiple sclerosis is a disease that impacts people differently depending on their age, their experiences, the course of the disease, metaphysical views (is staying alive at all costs an ultimate goal?) etc. Therefore, the boundaries of what we can accept or tolerate, in this world of MS filled with uncertainties, differ from person to person.
This is why I found the mantra that was repeated to me as the reason for refusing aHSCT (and I had active lesions after first line treatment) - "people don't die from DMT, HSCT is more dangerous" - unacceptable. First of all these doctors never gave me the opportunity to present my arguments on the "danger" (exaggerated because based on old data) of HSCT, nor on the fact that MS treatment goes beyond the control of active lesions visible on MRI. I was just told - "you don't need that".
My point is that today we refuse to administer a drug or launch a search for therapeutic solutions based on the notion of "danger" or "benefit-risk balance", not that of patients who know their limits of acceptability, but that of doctors who do not live with the disease on a daily basis and who do not necessarily have the same limits. One day I came across a comment saying "if a promising MS treatement carried a 20% risk of death, I would still be willing to try it because there are things I fear much more than death". 20% may be too much :) but this statement illustrates my point.
There are many MS patients who are willing to take the risk, as in the case of T-CAR for instance, the risk is not blind but after an explanation by professionals. But the killjoys refuse us this choice just because "you don't need it".
I wanted to say that I don't agree with the Killjoys. They have not walked a mile in our shoes. How can they ever get the daily., hourly, minute or seconds that Ms impacts on.
"These killjoys tend to be the same people who don’t agree with using AHSCT and alemtuzumab as a treatment for MS. Do you agree with them?"
I tells it how i sees it :)
https://substack.com/profile/94324668-anna/note/c-41832927?utm_source=notes-share-action&r=1k5pdo
I had mono 3 years ago at the age of 33. After 2 years I noticed first symptoms of MS. Usually it takes 7-8 years till the virus triggers MS. Is it possible that EVB starts to be "active" and drives MS so fast?
"what about crazy immunosuppressive anti-cancer therapies as anti-virals?"
What about anti-virals as anti-virals?
There seems to be a vanishingly small number of HIV patients on anti-retrovirals who have any kind of active MS.
There are plenty of anecdotal reports of patients on Tenofovir Alafenamide Fumarate (TAF, Vemlidy) not just NEDA but no PIRA (no progression / smouldering).
I'm trying to persuade my neurologist to let me try TAF. The other option (get myself infected with HIV or Hepatitis-B to force the decision) doesn't seem like a wise choice but desperate times necessitate desperate measures and time is brain etc.
Your first diagram is spot on and how there are the multiple factors in multiple sclerosis. The factors, in my opinion, are Genetics, Environment and EBV.
You can reach out to me and I can give you specific details around my family situation with this triangle of factors.
EBV = Epstein Barr Virus
What about someone with "naturally" low CD19 count in blood (in absence of previous DMD)? Would antiCD19 Abs still work or is CNS targetting agent better (only) option?
This is fascinating. I don’t think you are off the mark or single minded. At my age, new or more aggressive treatments aren’t an option, but herpes breakouts are constant - shingles, HSVs. I recall having mono as a child, perhaps 12? I never thought a thing about it until I became tired in my early 30s. I’m taking Valtrex now on a regular basis. A vaccine or a cure for EBV would be a truly amazing thing, particularly given your research with pw/MS. I’ve thought that if we have the zoster and HPV vaccines, how about some other HV vaccines? Thank you for your support and hard work for us. Please take care of yourself! (Delegate!) :)
Few questions - 1. could both theories of how EBV influences MS be true; 2. What cells EBV is infecting in CNS; 3. Aren't T-cells response increased for most when one is on Natalizumab?