[ME/CFS Research Foundation] International ME/CFS Conference 2026 7–8 May

MelbME said:
I wonder if someone will be game to do a CD19 CAR-T therapy on ME. That would be the ultimate test of the autoimmune hypothesis.
Click to expand...

Jonathan talked about CAR-T being quite hyped on another thread..
Jonathan Edwards said:
Firstly, I can assure you from years from now experience that people treating autoimmune disease do not have a clue about how to use rituximab intelligently. Rheumatologist have no clue about B cell dynamics - which is presumably why I was almost the only person to think of using rituximab for RA, lupus etc.. Oncology is quite different.

But that isn't the point. I have not seen good evidence for CAR-T working where rituximab did not work. There have been dramatic claims about cures lasting for ages for CAR-T but whenever Maria Leandro an I see presentations on this the data are no different from her results in 2000 on lupus with ritux. We had people staying well for years even then.

We know that depletion with standard ritux is not always complete, although for some of our cases it seems likely that it was and that the return of disease was because of survival of 'educator' plasma cell clones. I don't know of evidence on how complete depletion is with CAR-T. I suspect it may be similar - complete for some but not all.
Click to expand...
 
Braganca said:
Jonathan talked about CAR-T being quite hyped on another thread..
Click to expand...

The theory around why CAR-T would be better than Ritux is based on the hypothesis that EBV has close to immortalised a plasma cell tucked away somewhere. Ritux killing circulating B cells and then waiting 6 month for natural plasma cell death wouldn't work.

That's a simplification of the hypothesis of why Ritux may not work as well as CAR-T.
 
MelbME said:
The theory around why CAR-T would be better than Ritux is based on the hypothesis that EBV has close to immortalised a plasma cell tucked away somewhere.
Click to expand...

I don't think EBV is particularly implicated. It just seems that plasma cells can last for decades. Antibodies to vaccines tend to remain at reasonable levels throughout childhood even in those who are EBV naive as far as I know.

You can of course keep people B cell depleted for five years or more by repeat use of rituximab every 5 months and I have done that in severe RA cases. Antibody levels to tetanus tended to remain much the same. I am not sure that anyone has done it in cases of diseases like scleroderma that tend not to initially respond.

CD19 (or CD20) CAR-T would not hit plasma cells much I think.
 
Jonathan Edwards said:
I don't think EBV is particularly implicated. It just seems that plasma cells can last for decades. Antibodies to vaccines tend to remain at reasonable levels throughout childhood even in those who are EBV naive as far as I know.

You can of course keep people B cell depleted for five years or more by repeat use of rituximab every 5 months and I have done that in severe RA cases. Antibody levels to tetanus tended to remain much the same. I am not sure that anyone has done it in cases of diseases like scleroderma that tend not to initially respond.

CD19 (or CD20) CAR-T would not hit plasma cells much I think.
Click to expand...

There is an upswell of people believing now that EBV is the multiplier of all autoimmune disease and they see the CART success in Lupus as evidence. Every reactivation is another opportunity for EBV to spread to a different B cell with a different repertoire.
 
MelbME said:
There is an upswell of people believing now that EBV is the multiplier of all autoimmune disease and they see the CART success in Lupus as evidence.
Click to expand...

Yes, I keep away from upswelling people!! We don't even have any evidence for any special CAR-T success in lupus. You should see Maria Leandro smile behind her hand when she sees these 'new' data repeating 25 year old results.
 
Murph said:
I can't help but think about ORS, an intervention which killed loads of patients before they dialled in the dose exactly and it is now considered the greatest medical achievement of the 20th century, saving almost 100 million lives: https://www.amjmed.com/article/S0002-9343(24)00752-6/fulltext

(if you give cholera patients water: they die, if you give them salty water: they die, if you give them sugar water: they die, if you give strong salty sugar water: they die. But if you give them lightly salty sugar water they sit up, recover, get out of the hospital bed and go home.)

It's frustrating but in biology details matter so if you fail on one dose, sometimes abandoning the drug altogether is the wrong call.
Click to expand...
That was a matter of getting the chemistry right. If I remember correctly from reading about ORS a long time ago, you need the sugar to get the salt out of the gut without going through the normal salt route, which in turn made the water get absorbed faster.

It was the same for HIV drugs, where you needed to come at it from multiple angles. But none of that was figured out before you had evidence of efficacy in isolation, and people then tried to combine them to see if it worked even better. And it was all guided by insights in the pathology.
 
Last edited:
I wasn't sure where I should post this but I believe it should be posted here, given the presentations of the conference.

I spoke yesterday to two LongCOVID patients who have PEM after exertion. One of them (a psychiatrist) told me that he is witnessing LongCOVID being turned to Fibromyalgia as time passes by. After discussions, we realised that both of them have Gilbert's syndrome, a benign (??) problem of the gene UGT1A1 which impairs Phase 2 detoxification of the liver. One of them (the Psychiatrist) has consistently elevated blood ammonia.

Another patient told me -10 days ago- she has the HFE Gene (Hereditary Hemochromatosis - cc @Chris Ponting )

I read about neurons, CRH, CAR-T therapies, ME/CFS being associated with the brain -which is fine- but OTOH I see no actions for going back to the basics and investigating whether key metabolic perturbations exist in patients. I sincerely hope I am not the only one being deeply concerned about this.
 
What was also really interesting about the presentation by Michelle James was that her hypothesis is basically the same as the one from Mitodicure and Klaus Wirth. It would be interesting to know whether she came to that conclusion independently or whether she adopted it from Wirth. In her presentation, she definitely also mentioned this calcium overload and the resulting vicious cycle.
 
mariovitali said:
I see no actions for going back to the basics and investigating whether key metabolic perturbations exist in patients.
Click to expand...

As far as I can see researchers are still looking at metabolism and if anything more than ever with metabolomic and proteomic studies. The reality is that they are finding nothing that would account for symptoms. People tend not to emphasise negative findings when publishing but to me the negative data on metabolism is now pretty comprehensive.

In addition, the more I listen to people with ME/CFS the more I find it very difficult to explain symptoms on the basis of metabolic shifts. The timing of PEM and the longer term fluctuations seem much more consistent with signalling evens in nervous or immune systems. Some of us said that in our 'Biological Challenge' paper in 2016. (Fatigue 4(2):63-69. doi: 10.1080/21641846.2016.1160598. ) The DecodeME results look to me very much as we might have expected, although we would never have predicted the individual genes.
 
salin said:
Also of interest:
She confirmed that there will be an isatuximab trial.

(Wikipedia: "Chemically, isatuximab is similar in structure and reactivity to daratumumab; therefore, both drugs bind to CD38 in the same way. However, isatuximab exhibits greater inhibition of its ectoenzyme function. Isatuximab acts as an allosteric antagonist, inhibiting the enzymatic activity of CD38 in a dose-dependent manner.")

Unfortunately, this is only available to patients who have previously undergone immunadsorption.
I would have loved to have taken part...
Click to expand...
Did they say it about the IA (as it is not included in the inclusion criteria)?
 
Sorry if this is a redundant question, havent had time to follow closely. I vaguely remember from some lecture or presentation I attended a while ago that TSPO tracers have quite high binding affinity to some peripheral proteins. Idly wondering if this could be a possible explanation for reduced brain signal in James’ results. Would appreciate if someone could let me know whether the presentation mentioned anything about accounting for peripheral binding fraction somehow
 
You must log in or register to reply here.
Back
Top Bottom