41 Comments
Feb 22Liked by Gavin Giovannoni

I’d certainly volunteer for CAR-T trials. There are currently few, if any, drugs or treatments that seem to make a real difference in secondary progressive MS - so it’s worth finding out whether CAR-T therapy would or could help - or even potentially cure - MS. Anyone who thinks that SPMS is not ‘bad’ enough to warrant the risks of taking part in any trials has clearly not had to live through decades with a chronic illness that progressively eats away at our lives and our hopes. So many illnesses that we once thought of as hopeless or incurable are now either curable or at least modifiable. We are very lucky to be living in an amazing era for medical breakthroughs. We will be able to do so much more for people with MS if we can somehow manage to tailor those scientific breakthroughs to treat or modify this ghastly disease.

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Feb 22Liked by Gavin Giovannoni

I made a Facebook group for patients undergoig CAR-T treatment for autoimmune illness.

Some of te members have already had CAR-T done in Germany, USA, and China.

So please join the group

https://www.facebook.com/groups/cartautoimmune

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Feb 22Liked by Gavin Giovannoni

Yes I would be interested in participating in a CAR T-cell Trial. I suspect though that I will be considered too old to be a trial subject at age 60. Good luck I really hope a trial in MS can be achieved.

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author

And another editorial making the case for CAR T-cells in MS.

https://www.nature.com/articles/d41586-024-00470-5

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Feb 22·edited Feb 22Liked by Gavin Giovannoni

I would gladly volunteer for a CAR T- cell therapy clinical trial but I know at my age 56, that my demographic is almost always eliminated from a pool of volunteers for clinical trials.

***Edited to add, after having this miserable disease for decades, I really feel like I have nothing left to lose. I will try all the things if not for myself, at least for any people in the future having to live through this miserable disease.

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Feb 22·edited Feb 22Liked by Gavin Giovannoni

What are the possible risks? As I really don't have the time left in the course of my disease to either try or not to try anything without very good prospects VS extraordinary risks. Besides, I've already limited my chances of pulling through 'rough road' in any new treatments from all the stresses I have put on my genome from the myriad therapies I have tried already in the past twenty years.

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Feb 22Liked by Gavin Giovannoni

"we have such effective licensed treatments for MS"? What? Where?

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Yeah, that really chapped my hide too!

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Feb 22Liked by Gavin Giovannoni

I probably wouldn't qualify, since I'm between rounds of Mavenclad/cladribine, but I'd certainly be interested if I weren't.

The idea that there are neurologists who think the current state of play for MS is ok is straight-up horrifying.

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Feb 22Liked by Gavin Giovannoni

Right? I mean seriously? It is straight up horrifying!

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Feb 23Liked by Gavin Giovannoni

Prof. G - you are so right to reject the assertion of colleagues that "such" current effective treatments for MS justify precluding the use of Car-T trials. Frankly it is infuriating that some folks are seemingly happy with the status quo. I trust if they or their loved one had MS their views would shift. Thank you for your advocacy.

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Feb 22Liked by Gavin Giovannoni

After 25years, it is clear that the current medications do not stop this disease. I am personally not a risk taker, and have to take into account my school aged children, but sometimes the challenges that MS presents makes me think it’s time to take a big chance.

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Feb 22Liked by Gavin Giovannoni

Too risky for whom? I think the naysayers are risk averse and unwilling to discuss risk with their patients. Yes, I would volunteer to participate in CAR-T cell clinical trial.

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Feb 22Liked by Gavin Giovannoni

Thanks for this post.

“The good news is that three phase-1 CAR T-cell safety studies will be starting in MS, with several other companies planning to explore this technology in MS as well.” This is good news. But why is neurology always behind the pack eg rheumatology (lupus)? Tissue loss in MS much more devastating and irreparable.

“we have a battle on our hands to test CAR T-cells in MS. Many of my colleagues feel that this therapy is too risky for pwMS.” Your colleagues need to visit some care homes caring for those with advanced neurological diseases to really understand risk. Why would treating MS with Cart T-cells be more risky than for cancer or lupus?

Couldn’t the trial / experiment start really small eg 5 patients (no placebo) and see if the CAR T-cells clear OCBs in the spinal fluid?

With so many potential therapies on the horizon eg BTK inhibitors, Frexalimab, anti-virals, CAR T-cells, Ixazomib… any thoughts on which will have the greatest impact on smouldering MS?

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Feb 22Liked by Gavin Giovannoni

Although I've completed 3 “rounds” of Lemtrada, which appear to have ceased new disease activist (NDA), should I encounter NDA or progression I would love to have the option of an alternative highly effective treatment.

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Feb 22Liked by Gavin Giovannoni

100% agree with pressing ahead.

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Feb 22Liked by Gavin Giovannoni

I'm not sure about "EBV being necessary but not sufficient". As far as I'm aware there's at least one EBV-negative person without MS, that of course doesn't mean it doesn't play a crucially important role.

I would love to see a CD19 CAR T-cell trial in MS, go on press ahead with CD-19-targeted CAR T-cell therapies in MS! However, I expect that the above data will start becoming truely valuable once there is follow-up data has a duration of 5+ years. Then one will know more about the role of plasmablasts and B-cells. In the mean time, everything has to be set up to get the ball rollling once such longterm data is out, i.e. well done on getting the Phase 1 studies started!

The MS research community waited far too long to trial RTX, I hope they have learned from this mistake.

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Feb 22·edited Feb 22Author

There are very few pwMS who are EBV negative. In our hands it was only 1 case in over a 1000 cases. The majority of EBV-ve children with MS have now turned out to have anti-MOG associated disease and not MS. Please be aware that the diagnostic criteria for MS are not 100% sensitive or specific. Post-mortem studies have shown that 1 in 20 pwMS in life turn out to have another disease. So EBV-ve MS may not be MS.

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Feb 22Liked by Gavin Giovannoni

I certainly agree and see all these points, however that doesn't make the statement proven, 1/1000000 would still be enough for the statement to be wrong.

In any case, I appreciate your "EBV-advocacy" and can also appreciate somewhat harder claims that are true for almost all cases, especially when a majority of your colleagues are ignoring the EBV link.

I've been wandering if you know whether someone is working on replicating Ascherios work?

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Vietzen H, Berger SM, Kühner LM, Furlano PL, Bsteh G, Berger T, Rommer P, Puchhammer-Stöckl E. Ineffective control of Epstein-Barr-virus-induced autoimmunity increases the risk for multiple sclerosis. Cell. 2023 Dec 21;186(26):5705-5718.e13. doi: 10.1016/j.cell.2023.11.015. Epub 2023 Dec 12. PMID: 38091993.

I do have some concerns about this paper.

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Thanks, I've seen this paper and I have some concerns about this paper as well.

I don't think that this paper adds much to the Ascherio paper, is a replication or builds upon that paper to much.

The Ascherio paper was a gamechanger to me. To me this paper might just be false hope that leads nowhere...

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Feb 22Liked by Gavin Giovannoni

At 66 years old, I won’t be putting myself forward and my MS is reasonably well controlled on natalizumab with no recent relapses. Of course I realise it’s smouldering on but in my case it’s slow. I doubt sr my age I would be accepted anyway…. It is a highly interesting and exciting area of research

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