Reduced glycolytic reserve in isolated natural killer cells from ME/CFS patients: A preliminary investigation, Nguyen et al, 2018

https://www.ncbi.nlm.nih.gov/pubmed/29981562

The DOI (digital object identifier, aka ID number) for this doesn't seem to work, so I'm not sure anything beyond the abstract has been published yet.

 

According to the instruction manual for the Seahorse test used in this paper,

So the reduced glycolytic reserve seen in these preliminary results suggests the ME patients' NK cells have a significantly reduced ability to respond to energetic demand.

Eta: I wonder if some of this might possibly intersect with Booth and Myhill's work on mitochondrial ATP production.

 

Uncoupling of supply and demand ?
There could be a number of potential mechanisms?

 

I had ‘moderately reduced glycogen levels’ on my muscle biopsy even though I eat quite a bit of carbs. I am wondering whether this might be a common finding in ME in muscle tissue as well...

 

With the millions in funding this group has, it’s so frustrating that they often publish such tiny studies.

 

Pilot studies are meant to be small. It is designed so they can explore hypothesis without too much financial and human ressource investment. Since they seem to have found something, it will give them power to apply for some grants to either expand on a bigger cohort, or try the same experiment on other cell type, or compare to other similar diseases.

I am thankful that this team is exploring avenues that haven’t been researched through scientific experiments, through hypotheses and they are also teaching health science students about the disease. We need and deserve so much more research.

 

Yes, that’s the point I was wanting to make, but didn’t! Thanks, @Trish

 

The problem is success on a pilot study isn't actually statistically valid to justify further research, it simply shows that such an experimental design is possible.

 

So is this study consistent with the Newcastle University study? (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186802#sec007 - Figure 3E)

From my thirty second skim it seems to be pointing at least roughly in the same direction...

 

I think there is a definite intersection. They too found an uncoupling of supply and demand; more interestingly, for some they found that ATP was being flung out of the mitochondria faster than it could be replenished ( ostensibly due to substrate issues)- this could be ATP as puringenic signalling, instigating AMPK activation and downregulation ...

 

Jumbled thoughts:

Prof Don Staines presented data, at the Invest in ME Research International ME Conference 2018, indicating problems with calcium regulation. I assumed that they would/had published that data. I assume that the energy problems demonstrated in this paper are proposed to be a consequence of the calcium regulation problem.

This glycolysis study looks similar to other studies i.e. those referred to above (C Tomas etc); therefore, I'm not clear what's new. However, a study in effect confirming problems is still useful i.e. it increases confidence in the finding of energy/metabolic problems.

Ron Davis presented data at the Invest in ME Conference showing that you could potentially use the Seahorse analyser to diagnose ME/CFS.

Interestingly Ron Davis (in one of his talks - December 2017 OMF site?) said that ME/CFS did look like diabetes. Staines, at the Invest in ME Conference, said that TRIP receptors had a role in insulin regulation (diabetes). So possibly the calcium regulation (TRIP) theory Staines etc. are working on would explain the observed metabolic effects observed in ME/CFS.

I would like to see the calcium regulation data resented at the Invest in ME Conference published.

 

I think part of the problem is that this is a university where multiple PhD students need a novel hypothesis to research and report on and that is probably the main focus. I suspect finding answers to ME/CFS is probably a secondary goal.

 

Someone has to write the next grant -- and someone else has to approve it. Yes to the tiny PhD students trying to publish a thing -- and then moving on to the next thing, which may have nothing to do with ME.

At least theoretically, this is all you're supposed to need to apply for an R-level grant: show the experimental design works out, and show some promising results on a limited sample size.

I don't think Ron would mind if I pointed out that I mentioned if we called it "Type III Diabetes" that's when we'd get some real funding. I was only half-joking.

 

https://twitter.com/user/status/1028346685158817793

 

Hi Jaime, can you tell me more about how it looks like diabetes?