ME Association: ME/CFS researcher Cara Tomas explains the results from a new study on energy production and mitochondria

https://www.meassociation.org.uk/20...gy-production-and-mitochondria-14-march-2019/

 

I'm impressed with Cara Tomas and the team working with Professor Newton: they seem to be taking a steady, methodological approach to assessing whether energy production is impaired for ME/CFS patients and, if so, trying to locate where in the chain things are breaking down.

The findings mentioned here seem to tie in with those found by the Xinnan Wang Lab previously; that there is nothing wrong with mitochondrial energy production per se. This raises the question whether there is some kind of signalling issue that knocks out cellular energy production - which would be a massive find if true - or whether the energy production issues found so far are just the result of too many small-N studies and publication bias.

 

I have submitted this comment verbatim (including typos) because I believe this work is invalidated by using the Fukuda criteria.

This is a problem for ME charities funding CFS research and I believe it cannot be allowed to continue. Research must distinguish subtypes.

Of course the last bit should read "MRC" and "analyse" .

 

Haven’t multiple other groups already figured this out? What is new here?

It seems like this researcher is simply ignoring all the big energy dysfunction results that came out in recent years and is trying to reinvent the wheel?

 

Weren't they following up an earlier result that looked like it might have been something? Sounds sensible to me.

What research do you think they're ignoring?

 

Why would anyone who is genuinely attempting to research this disease use Fukuda?

 

It is widely used. I don't think that any of the criteria available are amazing, and I expect that they will all be superseded as research (hopefully) progresses.

Ideally we'd be able to get funding for research that allowed for sample sizes large enough that even if problems only related to a sub-group of one of the different criteria available we'd still be likely to find something.

 

Replication of earlier groups’ results is critical here: there is overlap between results but it is not 1:1. It is especially needed for metabolimics findings which so far have tested a large number of metabolites in a small number of patients, a recipe for inconsistency.

The idea that energy production findings are nailed down and thus any further studies are a waste of time is very misguided, in my view.

 

I wasn't aware that anyone had figured anything out. I would like to know if they have.
What is being ignored?

 

Very much this. A mito researcher I'm in contact with considers Cara's work a useful step forward in furthering our understanding of what is going on.

 

I did not say that or implying anything so broadly. The OP doesn’t mention larger study replication of previous results at all, its like the researcher is starting from zero.

Multiple previous studies have shown there is nothing intrinsically wrong with our mitochondrial genome and that we do not have a classical mitochondrial disorder.

This is what I meant by “already figured out”. Not that we already figured out all about ME mitochondrial dysfunction which of course, if said, would be misguided.

I do not think though that it is still a matter of debate if we have some form of inborn mitochondrial disorder, we don’t. The cause of ME would’ve been discovered long ago if this were the case.

 

I think my post is being misunderstood. I believe previous work has confirmed that we do not have an inborn mitochondrial disorder and there is nothing intrinsically wrong with our mitochondrial genome. This is what I meant be “figured out”.

 

My concerns are confined to cohort selection.

My suggestion would be, in the absence of a standardised way to subtype Fukuda patients, to repeat this study on mitochondrial function with a cohort selected in the same way as "cohort two" in the cognitive study, for whom a correlation between heart rate variability and impairment in digit-symbol-coding tests was detected, because this cohort provided statistically relevant results which were not apparent for the entire cohort "cohort one", indicating some kind of subtype.

It might even be possible to select a cohort based on whether patients showed this correlation, which would be a step towards developing more specific criteria for this subtype.


“Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction.”
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210394

It would not be safe to presume that noone with ME gets depression, but as a method for deriving a cohort it is simply a way of dividing the Fukuda cohort so that a subtype with ME like autonomic and cognitive symptoms becomes visible, when depression is excluded.

This would mean the mitochondrial data were not being diluted by results from different subtypes.

 

All the mitochondrial research to date where they already looked possible mtDNA mutations and performed other experiments on intrinsic mitochondrial function and found zero evidence of genetic mitochondrial disorders in PwME.

 

There were recent papers on this, but their study will have been designed a while back, and they were following up on there own work that indicated there might be something there. To me it seems worth trying to follow up on those sorts of things.

 

Unless my memory is playing with me I thought I read multiple studies looking into mtDNA mutations and potential mitochondrial disorders in ME patients going many years back, not just recently.

That technology has existed for a long time and was an obvious “low hanging fruit” research target for discoverying the underlying the pathophysiology of ME. No one ever found anything intrinsically wrong with our mitochondria and that’s why I wrote my original post asking why redo this experiment?

 

Fair enough.

 

You may be interested to watch Alan Light's presentation from Dec 2018

Here is one of the summary slides


In regard to mtDNA studies - my understanding from talking to others that just testing mtDNA is not sufficient - there are ~1000 nuclear genes that affect the mtDNA function

 

Nuclear genes encode for mitochondrial proteins. mtDNA also codes for mitochondrial proteins. Some complexes, for example, possess subunits encoded by both. It is definitely appropriate to consider both together in terms of using DNA centric methods to infer downstream consequences.