Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS),2021,Fluge,Mella,Tronstad

strategist said:
Thank you. I'm very curious about his views of ME as non-classical autoimmune disease.
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My pleasure. The translation was done very quickly during watching the lecture for the first time and with brain fog. I tend to loose a lot of vocabulary then, but hope at least main messages came through.

He says he can't find any of the typical tissue damage in ME patients which you would have expected in typical autoimmune diseases. No histologic inflammation. With pathogenic antibodies as in lupus, rheumatism, you will see tissue damage. He has not (yet) seen this in ME patients.

He went on to list everything they have done to look for specific autoantibodies in ME/CFS over ten years with no result.

ETA: Which was a quite impressive list on a slide at 31 minutes and includes a picture of him and his wife collecting pig tissue (dorsal root ganglion) at a slaughterhouse
 
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Kalliope said:
The Norwegian ME Association organised an ME conference last November in Oslo. They have now uploaded the lecture professor Øystein Fluge held on disease mechanisms in ME/CFS. I thought the paper he and his team published last spring was difficult to understand, and have missed a lecture for us patients. Finally here it is! But sadly only in Norwegian.

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Thanks so much @Kalliope for sharing this and for the extensive summary. Indeed pretty advanced and hard to follow but easier with Fluge's slides and your notes. I always appreciate the chance to listen to some Norwegian as well, it's like Danish but nice :emoji_upside_down:
 
Anders_Vang said:
Thanks so much @Kalliope for sharing this and for the extensive summary. Indeed pretty advanced and hard to follow but easier with Fluge's slides and your notes. I always appreciate the chance to listen to some Norwegian as well, it's like Danish but nice :emoji_upside_down:
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Glad you could follow the lecture in Norwegian as well. I feel their paper from last spring on their hypothesis on disease mechanisms for ME drowned in the pandemic and never received the attention it deserved. Otherwise I'd think some journalists would have gotten interested and we might have had some media articles helping with breaking it a bit down for us. Hopefully it's not too late.

ETA: Danish is much more charming to listen to than Norwegian, by far!
 
Kalliope said:
He refers to a study from 2020 titled "Diverse Functional Autoantibodies in Patients with COVID-19" which with a new technology called REAP (Rapid Extracellular Antigen Profiling) showed dramatic increase of auto antibody response after Covid-19. Could there be similar mechanisms in other infections?
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The study referred to:
https://www.s4me.info/threads/prepr...patients-with-covid-19-wang-et-al-2021.19230/
Kalliope said:
ETA: Danish is much more charming to listen to than Norwegian, by far!
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That's the first time I've ever seen anyone call Danish charming :rofl: Sorry folks, Scandi in-joke (and as a half Dane I'm allowed to joke about it).

ETA: very interesting talk, and good summary @Kalliope
 
Kalliope said:
Glad you could follow the lecture in Norwegian as well. I feel their paper from last spring on their hypothesis on disease mechanisms for ME drowned in the pandemic and never received the attention it deserved. Otherwise I'd think some journalists would have gotten interested and we might have had some media articles helping with breaking it a bit down for us. Hopefully it's not too late.

ETA: Danish is much more charming to listen to than Norwegian, by far!
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Indeed, pandemic news would have diverted some press attention from studies like this, for better or worse. I suppose to the degree Fluge et al's model might actually hold together as future clinical studies and research (by either themselves or others) seek to test its different components, the paper would gain renewed relevance and we'd hopefully see more accessible versions of the model itself. I liked how Fluge emphasised at the beginning that this is their best bet at a theory as of now, e.g. there is always room for error and refinements as things develop. Will be exciting to follow...

And a rare fan of Danish, lovely to see!
 
Marky said:
This part surpised me however:

"We speculate that cognitive techniques,
which are reported to help subgroups of
patients, might act by modulating the
sympathetic output. If so, one would
expect a greater benefit for patients with
less ongoing immune activation and less
vascular dysregulation, but with main
symptom contributions from the secondary
autonomic adaptations. Conversely,
patients with active immune disturbance
and ongoing vascular dysregulation as
the main symptom generators would have
less impact from cognitive intervention,
although psychosocial support and coping
strategies may still have a beneficial
impact on their quality of life."

That seems to be an significant leap of faith in terms of disease mechanism, dont really understand why they put it in there
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I guess if you read between the lines is he saying that cognitive techniques have no way of doing anything for ongoing/active immune activation and vascular dysregulation - so where these are generating the symptoms no difference would occur? But yes what is he including in 'secondary autonomic adaptations'? And what is he including in coping strategies?

- it could be as far as saying those who are mild and can do some things will get benefit from proper pacing/reduced exertion/better support and understanding around that as they can actually stay beneath their baseline and adjust to their disability, but I wouldn't call those 'cognitive', 'psychosocial'. I wonder whether it is 'this bit is off my turf, but this other bit it definitely doesn't work for'?
 
Campanula said:
This quote sounds very logical based on my subjective experience with the illness:
"We believe that the clinical symptoms in ME/CFS suggest inadequate autoregulation of blood flow according to the demands of tissues, resulting in tissue hypoxia. This is associated with lactate accumulation from limited exertion, in some patients even at rest."

Could it be that the fault is located on the brain level? The part of the brain that controls the blood flow in the body is the medula oblongata, according to this study, so it would be interesting if anybody knows if this part of the brain has been studied in ME before?

A fault in autoregulation of blood flow doesn't neccessarily have to be brain based of course, but it's one possible explanation, and not the most implausible based on my limited knowledge of these matters?
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I think that last line of yours is important. Just as they develop synacthen test type things to differentiate secondary from primary in those various illnesses, are there any mechanisms that could be probed to separate these out? I guess just like with those conditions it could be that there are different causes/issues for different individuals/types causing 'similar' outcomes? But maybe I'm showing my lack of knowledge?
 
So Chris Ponting checked the UK Biobank to see if the claim of an HLA association, in ME/CFS ("*" & "**"), applied to that (UK Biobank) cohort and it didn't - correct?

Seem to recall that the Norwegian group found an association with TPPP gene*** which also wasn't replicated in the UK Biobank (correct?). Still if we can identify a genetic signal for some people then that would be useful.
Wonder if selection criteria for Norwegian biobank would explain the difference and/or the genetic characteristics of the Norwegian group?

*"Association to specific HLA genes"
9.48 minutes from start
**https://www.nature.com/articles/s41598-020-62157-x
*** https://www.s4me.info/threads/genet...022-hajdarevic-et-al.25070/page-2#post-411286
 
Øystein Fluge held a presentation at RME last week (in English) where he goes through the findings in this paper:
YouTube: Pathomechanisms in ME/CFS - a model

Fluge and Haukeland University Hospital in Norway are now recruiting up to six patients to a pilot study where they will target plasma cells using the anti-cd38 monoclonal antibody medication Daratumumab. Study start date was 1 June 2022 and is set to end on 1 June 2024.
 
Cont…

https://twitter.com/user/status/1840294405170749453

https://twitter.com/user/status/1840294407448273023
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Edit: full transcript of BK’s thread:

For anyone interested in the pathophysiology of MECFS there’s a nice infographic here from this review article; https://jci.org/articles/view/150377 LOTS more research needs to be done of course. In clinical practice the vascular dysregulation is something I very much recognise​

Some of my bedbound patients have a raised blood lactate at rest, indicating that simply the energy required to stay alive has switched them into anaerobic respiration and oxygen consumption is outstripping supply 2/​

In less severe patients my colleague and friend @robinthephysio is finding reduced lactate thresholds, with patients switching from ‘green’ (aerobic) to ‘red’ (anaerobic) at low effort and heart rate levels - a key cause of PEM/PESE the cornerstone symptoms of ME 3/​

The root causes of this still need to be determined - immune dysfunction, mitochondrial dysfunction, endothelial inflammation, coagulation abnormalities, chronic infection or a combination. We need investment into the biomedical research 4/​

Challenges are that ME as a disease does not have a ‘home’ within a medical specialty as it affects all organs. Therefore there is no training of specialists, no academic research programmes and therefore very few grant funding applications being written 5/​

This requires the government and NHSE to start at ‘ground zero’, understandably it’s hard to know where to start with the scale of the problem and lack of specialists. We first need to get the right people in the room and have the right conversations 6/​

We start by doing ‘something’ not ‘nothing’ - as outlined in our letter the The Secretary of State, an immediate step is to create a commissioned clinical task force who can pull together treatment standards and guidelines (there are treatments!) 7/​

This would act as a group that could be consulted for advice if a severe patient ends up in a hospital with no internal specialists, or to support GPs to liaise with local hospital services. Once there are standards, organisations can be held to account for delivering them 8/​

We need CHC funding to extend to 24hour care for severely affected patients with ME. We need to create bespoke training for people caring for patients with severe ME. Technology could be used to support patients who are bedbound to monitor/communicate with their oversight team 9/​

We need to train a new generation of doctors to become ME specialists. Eventually aiming to have a specialist oversight and treatment team in each region 10/​

As all of this unfolds, we set up a national registry and start collecting data from across the country. This lends itself to real world treatment trials and fast-tracking translational bench to bedside’ research and giving patients access to drugs which might help them 11/​

I do hope Wes Streeting will meet with the #There4ME team. We need to political will and support to make this happen. A MASSIVE thanks to everyone who has supported the campaign so far and to @KarenLHargrave @GoreLloyd and @oonagh_cousins for their tireless work. END/


​
Edit: I’ve also posted this on the #ThereForME thread: https://www.s4me.info/threads/there...r-long-covid-and-me.39467/page-11#post-556306
 
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