Trial Report Plasma cell targeting with the anti-CD38 antibody daratumumab in ME/CFS -a clinical pilot study, 2025, Fluge et al

Anyway just a minor update from me. It is almost 7 weeks exactly have passed since dose 1 and I followed the protocol, with no side effects or adverse reactions, not falling sick.

Since my last test right after the 3rd dose, my IGG has halved and NKs have been wiped out.

Still feel tired, no major changes, no change in fatigue, but I feel some improvement in brainfog/cognition - however idk if it is placebo or not.

My fatigue is still bad and I wake up feeling like I slept 0 hours still.

Side note- in the study, I wonder if their sampling times like week 2,4,6,8 refer to the end of the week (aka the week has completed) or the start.

Again, I am still unsure if it is placebo or not. Unless it’s major change, then I can tell.
 
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I’m not well enough to digest all of this thread, and I don’t have the capacity or expertise to understand all of the science.

Can someone summarise in not too technical language what it would tell us about the pathology and mechanism of ME/CFS if daratumumab was shown to be an effective treatment for at least some people with ME/CFS.

For example, would it tell us that ME/CFS is B cell mediated in the subgroup of responders?

Would it tell us that were was something in the blood that, if identified, could be used for prognostic and differential diagnostic purposes?

Would it tell us whether ME/CFS (in responders) is an auto-immune disease?

What else?

I guess that in some cases it may just narrow down to possibilities of what the mechanism of ME/CFS might be in responders but I would be interested to try to understand what those possibilities would be.
 
Robert 1973 said:
Can someone summarise in not too technical language what it would tell us about the pathology and mechanism of ME/CFS if daratumumab was shown to be an effective treatment for at least some people with ME/CFS.
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Probably not @Robert 1973. There are a whole range of possible ramifications f a positive result. But in very simple terms it might mean B cells and antibodies are involved (maybe in some way we are not familiar with yet) and it might alternatively mean that activation of a whole range of immune cells, inluding NK cells, t cells and macrophages is involved, through a particular signal pathway.

But if the drug is effective it should not take too long to find out which.
 
EndME said:
I think for one the other CD19 and CD38 drug trials could then be informative on what differences, if any, might be driving responses.
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Yeah I remember isa maybe being better at depleting cd38 than dara or something? I can't remember, no spoons to look it up but I saved it somewhere.

It would be a real turn up for the books if cd19 works.

I'm glad CS seems to be moving swiftly with those trials.
 
Jonathan Edwards said:
There are a whole range of possible ramifications f a positive result. But in very simple terms it might mean B cells and antibodies are involved (maybe in some way we are not familiar with yet) and it might alternatively mean that activation of a whole range of immune cells, inluding NK cells, t cells and macrophages is involved, through a particular signal pathway.
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I know I’m getting ahead of myself here but do you think it is likely that whatever novel mechanism is revealed is likely to further our understanding of other diseases, and therefore our ability to treat them?
 
Robert 1973 said:
I know I’m getting ahead of myself here but do you think it is likely that whatever novel mechanism is revealed is likely to further our understanding of other diseases, and therefore our ability to treat them?
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Very likely, even if the other diseases are a bit esoteric.
I have a feeling that if we can understand ME/CFS we may have a better understanding of all sort of diseases though.
 
Jonathan Edwards said:
Very likely, even if the other diseases are a bit esoteric.
I have a feeling that if we can understand ME/CFS we may have a better understanding of all sort of diseases though.
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But isn't MECFS (because that's what we have to call it) ultimately a post-viral syndrome or a shock to the central nervous system/hypothalamus that disrupts most of the body's systems (vascular, neurological, immune, RAAS, hormonal, mitochondrial...)? The luckiest have one or two systems disrupted; the body tries to compensate as best it can, but in very severe cases, when everything has exploded, could an anti-CD38 or even an anti-CD19 correct this whole mess? I wonder if we really have a disease, or rather a critical disruption of the systems that are supposed to regulate the body... can we even call it a disease with such heterogeneity? Is PEM really enough to unite everything (like in Lord of the Rings)?
 
neophyte32 said:
But isn't MECFS (because that's what we have to call it) ultimately a post-viral syndrome or a shock to the central nervous system/hypothalamus that disrupts most of the body's systems (vascular, neurological, immune, RAAS, hormonal, mitochondrial...)?
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I don't think we have any evidence for any of that much. ME/CFS can follow viral infection but it can occur without as far as we know. I am not sure what a 'shock' is. I prefer to talk of specific pathways. I don't think we have any evidence for it disrupting any systems except the central nervous system, which is where all the symptoms ultimately arise. I haven't seen any good evidence for vascular changes, other than maybe responses to neural signals. We don't know that there is any ongoing immune disruption but if there is it is probably what started thigs off in the first place. I don't know what RAAS is. Hormones and mitochondria lok fine to me...

I do think we may have some major clues. It seems that certain immune signals can get things started. Interferons might be involved. It seems that there is a persistent problem with central nervous signalling, but exactly which symptoms that explains and in what way is very unclear. And we don't have any specific handle on what keeps the abnormal state going. For autoimmune disease we realised that you can pinpoint very specific pivot signals for each disease, each with a potential built in Achilles heel. Exactly how the fault works we still don't know for most diseases but we have an understanding of how it might work. For ME/CFS I don't think we are there yet, but we might be nearer than we think.
 
Jonathan Edwards said:
I don't think we have any evidence for any of that much. ME/CFS can follow viral infection but it can occur without as far as we know. I am not sure what a 'shock' is. I prefer to talk of specific pathways. I don't think we have any evidence for it disrupting any systems except the central nervous system, which is where all the symptoms ultimately arise. I haven't seen any good evidence for vascular changes, other than maybe responses to neural signals. We don't know that there is any ongoing immune disruption but if there is it is probably what started thigs off in the first place. I don't know what RAAS is. Hormones and mitochondria lok fine to me...

I do think we may have some major clues. It seems that certain immune signals can get things started. Interferons might be involved. It seems that there is a persistent problem with central nervous signalling, but exactly which symptoms that explains and in what way is very unclear. And we don't have any specific handle on what keeps the abnormal state going. For autoimmune disease we realised that you can pinpoint very specific pivot signals for each disease, each with a potential built in Achilles heel. Exactly how the fault works we still don't know for most diseases but we have an understanding of how it might work. For ME/CFS I don't think we are there yet, but we might be nearer than we think.
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Thank you, Professor. Regarding mitochondria, many of us have had tests done in Germany or England, and they're completely depleted... RNA sequencing shows that numerous pathways appear to be totally dysregulated. Shouldn't we be concerned about this, in your opinion? Could treatments like Daratumumab act on all these cascading systems? Because there must be a reason why our bodies seem so utterly destroyed...
 
Jonathan Edwards said:
Very likely, even if the other diseases are a bit esoteric.
I have a feeling that if we can understand ME/CFS we may have a better understanding of all sort of diseases though.
Click to expand...
Kitty said:
This is what frustrates me about the failure to fund projects like SequenceME & LC. It's hard to understand why they don't see the opportunities.
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Yes, if only we could only get the funding bodies to understand, but I fear we will need a breakthrough before the scales to fall from their eyes, which is something of a Catch 22.
 
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