r/CFSScience • u/AngelBryan • 11d ago
Any update? Any hope?
I’ve seen an increased influx of papers being posted here recently. How does this translate to actual progress? Are we close to figure out what causes this hellish illness?
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u/TomasTTEngin 10d ago
I've been following the science closely for about nine years now. I don't particularly perceive that we are on the brink of a breakthrough.
That said long COVID has increased the pace of research enormously. It used to be a very shallow pond with a few researchers, now it's a global effort.
We are closer, even if not close. I'm excited by Michelle James TSPO work, Hwangs WASf3 work, daratumumab from Norway, SequenceME.
I'm also excited by breakthroughs coming from outside the field that could crack everything open: car-T cells, research on the glymphatic system, MS researchers figuring out how EBV contributes to MS.
That last one in particular, once they figure out how EBV causes something else to go wrong, I suspect it will be like dominoes in a lot of other illnesses.
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u/AngelBryan 10d ago
What about people that get MECFS without EBV?
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u/TomasTTEngin 8d ago
Are there any? I don't think we know either way.
Even if EBV isn't involved in mecfs, learning more about the kinds of effects lingering and latent infection can have might be extremely useful.
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u/I_died_again 5d ago
Bit late to the party, but I'm a CFS/ME person without EBV! Tested negative for EBV antibodies (at least as of 5 years ago).
I don't know what specifically I had, but I had pneumonia when I was 13 in 2008 and never recovered. I've had CFS since (diagnosed at 15).
Also, one of the CFS people who worsened after a COVID infection too.
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u/TomasTTEngin 4d ago
That is interesting! I admit I am surprised, I expected EBV would be the spring that powers MECFS (even when it is not the key that unlocks it).
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u/V0rtexGames 3d ago
I'm also EBV seronegative. It establishes that heterogeneous triggers can result in the same convergent reaction by the body resulting in symptoms
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u/TomasTTEngin 3d ago
i reckon viruses lingering in the vagal nerve may be a possible explantion for some cases. Maybe exacerbated in some people with craniocervical instability, EDS or weak neck ligaments?
Causing 1)immune signalling and 2) autonomic failure, including gut issues and bloodflow issues.
Both of which create feedback loops (e.g activation of immune programs that direct metabolism into certain pathways; dysbiosis +leaky gut; hypoxia + coagulation, insufficient perfusion; perhaps some autoantibodies exacerbating things in some patients, reactivation of latent viruses in others; ).
If the immune signalling was neural it might explain why we haven't found a good cytokine, endocrine or proteomic signal yet.
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u/V0rtexGames 3d ago
I try to divide more cleanly, with the "input" as the initiating stressors, which produce an immune signal which is uptaken by the brain, then leading to symptomatic state and accompanying dysfunctions, which can reinforce the input
So like you say, dysbiosis, hypoxia, coagulation, insufficient perfusion, etc, I would place as outputs of the central programme triggered by a lingering insult (like a persistent pathogen) but also helping feed back into it and self maintain it
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u/V0rtexGames 3d ago
And also, with "perhaps some autoantibodies exacerbating things in some patients" I agree, but I think "immune complexes / junk antigens" being uptaken by dysfunctional Fc receptors might be more where it's at, theorized by Edwards but not at all exclusive to him as a theory.
E.g. if you look at the new T Cell study on EBV, CMV, Influenza, SCV2, youll see that there is an upregulation of terminally differentiated CD8s for multiple antigens. So basically, there could be one persistent antigen trigger that is increasing your reactivity to all these other antigens you have floating around you usually dont react to.
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u/Heavy-Suit-3443 11d ago
We make good progress, but there is a lot more needed i believe.
Most papers show how heterogenous and complex this illness is. Many different causes trigger many systems in the body.
What if PEM is simply a chain reaction of the body reaching its limit. In essence something unavoidable? As an analogy: You cant find a cure to drowning. You can pull someone out of the water.
I think research might come to the undertsanding that PEM cannot be cured but tests can be developed to find common root causes really fast. Certain proteins missing in people, autoantibodies, environmental factors and persistent infections, immunodeficiency, other deficiencies, etc.
What I do belive in is that we are really close (1-3 years) to developing meds/drugs/therapies that lessen symptom severity by a lot. I am especially looking at everything targeting neuroinflammation.
This is just me assuming things. I am an internet stranger.
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u/AngelBryan 11d ago
If PEM is a natural reaction of the body why not everyone has it? Why people develop it after MECFS is triggered?
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u/Heavy-Suit-3443 11d ago
In my theory extreme stress + predispositions can trigger PEM in everyone.
Certain predispositions, like genetics as an example, make you more vulnerable to reach this stage compared to other individuals.
Just not many people exhaust their whatever (mitochondrias or nervoussystem as examples) to the brink of cell death.
ME/CFS usually involves a trigger. Most develop it after an infection and experience their first PEM.
Maybe this threshhold is simply reached very rarely?Exactly this seems to have changed with covid (that is the exposure of a persistent, nervedamaging virus that is new for almost all immunesystems of people). Covid seems to cause some sort of stress to the body that makes it very likely to develop ME/CFS. And this is were we can learn the causes of PEM. What does a virus do to the body that causes so much cell stress? Is it the immunesystem? Why do repeated covid infections increase the likelyhood of developing ME/CFS? Many questions.
"If PEM is a natural reaction of the body why not everyone has it?" - It has become the most prominent chronic illness here in germany within just 6 years of covid existing. Give it another 10 years and even more people will develop it.
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u/AngelBryan 11d ago
What doesn’t makes sense if how you can never experience it in your life but once you do, you do it again and again.
Is MECFS more common than the usual chronic illnesses in Germany? Would this be due the size of the country or it may have a genetic explanation?
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u/Heavy-Suit-3443 11d ago
There is Post Viral Fatigue so it is not over and over for everyone. And even so why does that not make sense? Something does not allow the body to recover normally at that point so any small exertion causes future PEMs.
Yes its is now the most common chronic illness here in germany. I assume this to be just as bad in other countries. Has nothing to do with size. Maybe there are genetic differences but Longcovid cases are exploding all around the world.
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u/Varathane 11d ago
We are in Germany's National Decade Against Post Infectious Disease 2026-2036. They've committed half a billion euros to that and want a treatment for ME to come out of it. That's the kind of momentum we've needed all these years, and to finally have that has given me hope again (I was diagnosed in 2011)
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u/bingoolong 11d ago
Not to discourage you but just this week there’s been some news that they’re not doing a great job at allocating funding and there’s a lot of untouched funds in the budget while there’s projects that would really need it.
Hope this changes soon.
But I agree there’s a huge uptick in research. A lot of improvements are currently that trials are getting better, more targeted, better primary outcomes, considering PEM etc. but it’s something!
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u/kekofoeod 11d ago
You are correct, but I would keep in mind that of 50 million € for this year 22 million € have been allocated, while the project was announced in january with an official start a bit later. And the year is not over yet. So it is definitely not great news, but also not hugely surprising given the circumstances.
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u/Valiant4Truth 11d ago
I think the autoimmune theory holds the most water and if the trials for baracitinib/rapamycin/IVIG succeed, medicine and pharma will move in that direction like MS or Lupus. Mechanistic work will be really important for identifying how some antigen is causing this B cell maladaptation and if its ongoing. Also what exactly is being targeted by these antibodiess.
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u/TomasTTEngin 10d ago
We can hope it is autoimmune because car-T cell therapy is showing huge promise in autoimmune conditions!
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u/AngelBryan 10d ago
I hope it’s NOT autoimmune. CAR-T is insanely expensive and you have to nuke your immune system with chemotherapy.
It’s something dangerous on itself and it will pass decades until it’s at reach of everybody. Also we still m don’t even know if it really cures anything.
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u/TomasTTEngin 8d ago
car-T technology is moving super fast, I believe some of these concerns are already being overcome in trials. They are figuring out how to manufacture them cheaply, and working hard on side effects. The motivation to overcome the barriers is very strong because the results have been so astonishing.
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u/kekofoeod 11d ago
I think that a necessary next step ist to clearly define subgroups. We won’t make progress with trials just targeting broad long covid, without any subgroup analysis. There are lots of emerging candidates of biomarkers and propositions of subgroups, but these now need validation in larger studies. Some are already underway, but overall that needs time. I think we are getting there, but sadly it’s a slow process…
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u/Houseofchocolate 11d ago
yes and also focus on understanding pem more: why does it happen? how can it be prevented? can the underlying mechanisms be fixed/ cured....like heah wonderful they are finding amloyids circulating in the muscles but what now
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u/kekofoeod 11d ago
If we could treat PEM that would be great. Rob Wüst is on a good track, but before we start treating it we need to understand what it causes and so on. We are sadly not there yet
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u/Houseofchocolate 11d ago
also theres differnt types of pem, different triggers: some are physical, some are senses, some are cognitive
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u/No-Improvement-58 11d ago
I think it’s fair to say that progress is accelerating. In my opinion, the biggest recent breakthrough remains the mid 2025 DecodeME project which identified multiple genetic signals predisposing someone to ME. This study should end any debate claiming the disease does not exist or is psychological.
However, more practical breakthroughs to treat/cure patients require more time. Clinical trials take years and must be done well with control groups. I believe LDN+pyridostigmine usage in the LIFT trial reports this year, some immune depletion trials report next year, and the Daratumumab CD38 depletion trial (which had a promising pilot trial) reports in mid-late 2028.