In your opinion, what has changed, if anything, in ME/CFS research in the last 10 years? If it has, what do you think was the catalyst?

From a german perspective, in Germany there has been a lot of change in the last 10 years.

While Prof. Scheibenbogen‘s work is often doubted/ criticized on here, she remains (in my opinion) Germany‘s biggest factor for this change.
She started seeing ME/CFS patients in Berlin almost 20 years ago- and for many many years she probably was the only public figure speaking out and advocating for us.

For example, when I became ill in 2020, I knew that I had ME/CFS 3 months after symptom onset because of her many articles and interviews and youtube videos.

Alongside with patient organizations and COVID which led to many many more ME/CFS patients, the game changed.

Many people became involved in advocacy, there are now likely 20 ME/CFS patient organizations in Germany like Liegendemo, Deutsche Gesellschaft für ME/CFS, Fatigatio, etc. (in my opinion there are too many).

Step by step funding became available.
The NKSG.
Then Through the BMG (care and treatment center- projects) and now the National Decade against post infectious diseases.

And also the ME/CFS Research Foundation and more allocation of private funding.

It remains to be seen how groundbreaking or not the „Decade“ will be.
 
neophyte32 said:
I have only been ill since 2022, so I am still relatively new to the history of ME/CFS — although, in my experience, every month spent severely ill can sometimes feel like several months in the moderate stage, simply because the level of suffering and restriction is so extreme.

I often wonder what ME/CFS research was really like before 2020. My own research only began in March 2025, when I finally understood what was happening to me.

At the time, I kept coming across the same names and the same hypotheses: the Davis family, the Itaconate Shunt, Klaus Wirth’s work around mitochondrial dysfunction, viral persistence with Putrino, PolyBio and others. I completely missed the whole BC007 episode — and, looking back, perhaps that was not such a bad thing.

I have the impression that 2025 was an important year. There was DecodeME, the work published by Fluge and Mella and several other studies that I found particularly interesting, including the study involving autopsies of the brains of severely affected patients.

But one question keeps bothering me, and perhaps it is a naive one : why do some of the best-known researchers sometimes seem to pursue their own particular avenue almost independently of what is happening elsewhere ?

I was struck, for example, by how little attention DecodeME sometimes seems to receive in the public discourse of otherwise highly influential researchers: Scheibenbogen, Wirth, Davis, PolyBio, West, Putrino, Iwasaki, Lipkin, Klimas... I remember reading an interview with Nancy Klimas and getting the impression that she remained very focused on her own therapeutic trials — Sipavibart, probiotics, and so on — without really integrating what DecodeME might change in the way the disease is understood.[........]
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I think the answer for this is partly what you describe in the part of your post I am not quoting here and partly it's a little different for each researcher.

Scheibenbogen for example, with all due respect for her advocacy work, is absolutely trapped by her autoimmunity and b-cell ideas; I can't imagine her paying more than passing attention to anything else before she has either proven that some people profit of the treatments she suggested for the last 10 years or money for such trials dries out.

Wirth doesn't just have a theory but also has his own company and pharmaceutical products he's trying to secure funding for, I can't imagine him being interested in things not tied to his products.

Davis is, with all due respect, very old and doesn't have much funding compared to Scheibenbogen, Polybio or even Klimas, so I think he is rather limited in what he still is able to do and his own projects seem to absorb him completely.

And some other researchers never really looked into ME/CFS beyond a vague "phenotype" of long COVID, they often also don't seem to be far-sighted enough to understand the implications of DecodeME.
Their primary motivation also doesn't seem to be the production of solid science and evidence, but to get anything into people's hands as quickly as possible so they no longer feel so help- and powerless themselves—whether that's Rapamycin, HbOT, LDN or some trendy gadget and no matter of it really works or doesn't. And if that's your goal DecodeME isn't really of much interest for you.

So I think there are various reasons why some of the best known researchers don't seem to give the findings of DecodeME much attention.
 
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Silip said:
Wirth doesn't just have a theory but also has his own company and pharmaceutical products he's trying to secure funding for, I can't imagine him being interested in things not tied to his products
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I can’t comment on this any further- but I know for a fact that Wirth is interested in ME/CFS as a whole, not just in his company and products.

It’s just that this is his lead- and he thinks he could be right. I‘m pretty sure he still reads all the literature and studies and preprints.
 
Robert 1973 said:
And I think I'm right in saying that @Tom Kindlon was instrumental in getting Dave involved
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Well, his work had a big impact on me!! What happened here was that I needed to figure out a narrative structure to tell the story of the trial. It was so complicated and I needed to find an effective way to keep people reading, given the length. (I'm sure many couldn't get through the whole thing.) Tom's work had left a paper trail across many years in letters to journals, articles, etc that could be cited and quoted to help move the story along. So I chose him as a "protagonist" of sorts through which to build a narrative. And luckily, Tom was willing to trust me and go along with it, and spend lots and lots of his time and energy talking with me. I'm sure the effort took a lot out of him but I was enormously grateful for his input.
 
justlxsa said:
I can’t comment on this any further- but I know for a fact that Wirth is interested in ME/CFS as a whole, not just in his company and products.

It’s just that this is his lead- and he thinks he could be right. I‘m pretty sure he still reads all the literature and studies and preprints.
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Yes, I probably didn't word this correctly. What I meant wasn't that he personally isn't interested in the literature or other ME research in general, but that I am pretty sure he doesn't plan to pursue other leads not tied to his company in the near future. Furthermore when I read his papers and thoughts I always do this while keeping in mind that he has a product to sell.

This isn't necessarily only a bad thing, as long as someone plans that his product undergoes a serious scientific process I'd say people trying to get involvement from pharma and attract investment in ME research from outside the traditional humanitarian circles is something I like to see.
 
Jonathan Edwards said:
The impact will come because the leads will take us to the answers. What is a bit disappointing to me is that people here think DecodeME was disappointing. I am not sure what was expected.
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While I'm immensely grateful for DecodeME, and very hopeful that it points the way to the answers, the aftermath has been disappointing in the sense that you were predicting last year that we were going to understand what MECFS is by the end of the year, that there would likely be drug targets etc.

And then it turned out that the HLA peak was actually BTNs, the HLA analysis came up with nothing, the tissue analysis was all neurons, and we can't find any BTN experts to investigate that trail, which might be the only major clue we currently have towards figuring out if there is any immune pathology, among other ways it could lead. The only drug targets that emerged were the ones PrecisionLife provided which turned out to be half hearted recommendations for LDN and Ampligen. And sadly while we might have some good new or improved ideas about what MECFS could be, we certainly do not now know what it is.

Its great that we have progress and that DecodeME proves that MECFS is a real syndrome (although it doesn't seem to have got through to doctors or funding bodies). Hopefully it will be the start of a revolution in MECFS research. And we still don't have that X chromosome analysis which could be really interesting.

But even though the rediscovery of those papers happened after DecodeME was published, we currently can't find a clinician to do a new trial of the buspirone challenge despite the fact it's crying out for replication and further investigation. We still can't convince funding bodies and charities to fund all of SequenceME, even though it is clearly a brilliant project that could deliver everything we hoped for that hasn't materialised. We still have brilliant scientists on here who are struggling to find funding. We still face suspicion, bafflement and hostility from doctors etc every time we interact with them.

So surely you can understand why a community of people in desperate situations, who need a major breakthrough and the legitimacy and treatments it would bring yesterday, would be disappointed that none of what you were predicting last year has come to pass?

Please don't interpret this as me having a go. I have no animus towards you - you were just reacting to the scientific picture as it emerged. I'm just trying to explain why some of us might feel disappointed in how things have shaken out.
 
V.R.T. said:
While I'm immensely grateful for DecodeME, and very hopeful that it points the way to the answers, the aftermath has been disappointing in the sense that you were predicting last year that we were going to understand what MECFS is by the end of the year, that there would likely be drug targets etc.
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I am not sure that I was that explicit. Nonetheless, I suspect we do now have a fairly good idea of what ME/CFS is - a problem with synaptic maintenance - even if we need a lot more information to flesh that out. And there are potential drug targets within that.

Part of the problem is that the DecodeME team have been hamstrung by the security leak. I could not have predicted that.

V.R.T. said:
And then it turned out that the HLA peak was actually BTNs
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But in a way that made things simpler. We did not need to be distracted by antibodies. And since BTNs clearly do something special in parts of brain it again simplifies the overall picture.

V.R.T. said:
But even though the rediscovery of those papers happened after DecodeME was published, we currently can't find a clinician to do a new trial of the buspirone challenge despite the fact it's crying out for replication and further investigation.
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That may already have changed.
 
V.R.T. said:
So surely you can understand why a community of people in desperate situations, who need a major breakthrough and the legitimacy and treatments it would bring yesterday, would be disappointed that none of what you were predicting last year has come to pass?
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At least as much as I actually predicted has come to pass in my view. I realise that everything still seems up in the air, but we have several quantum leaps in understanding. I have been in this situation before. You keep going and make progress despite the hostilities and stupidities.
 
Jonathan Edwards said:
I am not sure that I was that explicit.
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You were pretty explicit. But as I said, you were reacting to the emerging picture. I think we were all hopeful the DecodeME data would line up with the Fluge and Mella and the Wessely genetic data on HLA, the dara pilot, your hypothesis etc. I'm not having a go, just pointing out that in the sense that those things haven't come to pass, the aftermath of DecodeME has been disappointing. Even if there is lots of hope in other senses.

Jonathan Edwards said:
Nonetheless, I suspect we do now have a fairly good idea of what ME/CFS is - a problem with synaptic maintenance - even if we need a lot more information to flesh that out. And there are potential drug targets within that.

Part of the problem is that the DecodeME team have been hamstrung by the security leak. I could not have predicted that.


But in a way that made things simpler. We did not need to be distracted by antibodies. And since BTNs clearly do something special in parts of brain it again simplifies the overall picture.
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You may be right about the BTN situation simplifying things. I'm still interested in the idea that it might be playing a dual role in brain and immune tissue. I didn't know that there were already potential drug targets in terms of the brain stuff but I'm really glad to hear that's being thought about. Are we sure we can say it's synaptic maintenance rather than some other issue with neurons?

Yes the security leak has been an unexpected and frustrating development. My understanding is the team should have access again this month which is good.

Very glad to hear about the buspirone situation changing! And glad you're still optimistic.
 
V.R.T. said:
I think we were all hopeful the DecodeME data would line up with the Fluge and Mella and the Wessely genetic data on HLA, the dara pilot, your hypothesis etc
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I don't think that was my mindset . I think I was hoping for something more unexpected - which is what we got. An HLA-D link would not have fitted particularly with the hypothesis I published with Jo and Jackie and that was always more an exercise in laying out the things to answer than a claim to have an answer.
V.R.T. said:
Are we sure we can say it's synaptic maintenance rather than some other issue with neurons?
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I suspect that synaptic maintenance is the only thing that would make much sense anyway. A shift in function of a large enough number of neurons to produce an acquired illness with the impact of ME/CFS could be explained by shifts in synaptic maintenance and I am not quite sure what else. It could still be downstream of T cells signalling around the base of the brain. Cells are not dying as far as we can see and there is no inflammation evident.
 
Jonathan Edwards said:
I don't think that was my mindset . I think I was hoping for something more unexpected - which is what we got. An HLA-D link would not have fitted particularly with the hypothesis I published with Jo and Jackie and that was always more an exercise in laying out the things to answer than a claim to have an answer.
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Ah ok. Yeah I guess that was more my mindset! Or one of them. I shouldn't have zoomed in on that specific idea or set of them anyway, as I was talking about the more broad hopes for rapid progress in terms of understanding and drug targets. But I'll leave it here for this discussion and focus on the present.

Jonathan Edwards said:
It could still be downstream of T cells signalling around the base of the brain.
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A random thought- many people with MECFS, including myself, report pain around the base of the brain in PEM. Could this be related?

And do you know if there is any way to image T cell activity in the base of the brain?
 
Professor @Jonathan Edwards, could your hypothesis of a problem with “synaptic maintenance” in ME/CFS help explain PEM ?

I’m thinking particularly of the fact that exertion can sometimes be relatively well tolerated at the time, only to be followed several hours later by a significant and prolonged worsening of symptoms. Could excessive exertion overwhelm the recovery capacity of certain neural circuits, potentially helping to explain both this delay and the abnormally slow recovery ?

I’m also curious about the post-exertional episodes that some patients describe as “panic attacks”: a sudden sense of danger, dizziness, profound malaise, tachycardia, and sometimes hyperventilation, without any obvious psychological trigger. Do you think these could reflect a post-exertional autonomic or neurological reaction, possibly related to the same synaptic maintenance problem ?

One last question, perhaps a slightly provocative one : are you genuinely optimistic about where the research is heading, or is there also, as a researcher and professor, an element of trying to give us some hope, knowing how desperate many patients have become ?
 
neophyte32 said:
I’m thinking particularly of the fact that exertion can sometimes be relatively well tolerated at the time, only to be followed several hours later by a significant and prolonged worsening of symptoms.
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I think the consistency of PEM delay is important. Could a "synaptic maintenance" theory explain the consistency of that delay? I've always considered the consistent delay as explained by immune system delay.

This question is muddied by PWME who have shorter, inconsistent delayed response to exertion, which might not be the same mechanism as the common 24 hr delay PEM.

My cognitively-induced PEM had a much shorter (could be less than an hour) and more variable delay. I attributed that to neural activity affecting the ME mechanism directly, rather than through t-cells or whatever. I still have a feeling that glia are involved: responding to delayed immune signals, or more directly from neural activity.
 
neophyte32 said:
I’m thinking particularly of the fact that exertion can sometimes be relatively well tolerated at the time, only to be followed several hours later by a significant and prolonged worsening of symptoms. Could excessive exertion overwhelm the recovery capacity of certain neural circuits, potentially helping to explain both this delay and the abnormally slow recovery ?
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I would think more in terms of synaptic reinforcement leading to an increased sensitivity of neuroendocrine pathways that might take several hours to generate signals - like the prolactin response to buspirone maybe.
 
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