The nanoneedle salt stress test – too good a clue to leave abandoned on the lab bench?

A few thoughts

I don't understand why tenure was quite so big an issue. Every academic wants tenure as it gives them security for the rest of their career. But I think it's unusual to get it very early on, and not getting it quickly doesn't cost you your job - you just don't have job security locked in. Rahim Esfandyar-Pour still has his job and his lab. But of course, it is entirely his choice what work to pursue, and he already did the ME community a favour with his early nanoneedle work.

I realise that Ron Davis has very high ethical standards, but as someone with an awful disease, I wish there had been a way to follow up on the initial findings (that no longer seems possible as RE is no longer responding to RD).

It is very good this is now being followed up in the UK. I hadn't realised that Prof Robert Dorey was a nanomaterial expert (though not in medical applications), which is great.

Exactly. It was the spectacular differences between patients and controls, with clear blue water between them, that was so compelling. I appreciate @Jonathan Edwards's concerns, but I still want this finding followed up robustly.

And I am excited about this, not least the focus on understanding any pathology behind the differences. If those differences are indeed real. With such a big effect, you might expect the underlying biology to be a big clue to a cause of MEcfs.

 

That's my big worry, that it was almost too good to be true. Can't think of other ME research that had such differences between patients and controls. My other big worry that this is the real reason progress hasn't been made, it was just an artifact of the testing and Ron has realised this and let it quietly fall away.

 

Yes, me too. It may turn out to be an artefact or error, but someone needs to show that before it can be abandoned.

Even if it picks up evidence of an energy limitation but can't reliably discriminate one disease from another, it's still important.

 

Has anyone not affiliated with RD tried getting in touch with RE to find out why this project was abandoned? I always assumed it didn’t pan out in subsequent testing so they just quietly dropped it (like a bunch of other things they used to talk about but don’t anymore). So, this news of an independent replication in the UK seemingly out of nowhere is very surprising.

 

Surely the charities must have known more before deciding to allocate funding? But perhaps not?

 

I am not sure that in this situation it is ever possible to 'know' much more. The results of the original study are out there. No information is available as to exactly why it was not followed up and nobody can be forced to provide that.

The charities use people like me to judge whether or not repeating such studies - or doing similar experiments that might corroborate the findings - is worth investing in. I agree with Simon that whatever the uncertainties, an attempt to confirm has to be worth at least a small investment. One has to trust that researchers will do their best to get a genuinely meaningful result.

 

Thank you for your helpful comment @Jonathan Edwards.

 

I did wonder about that, but I don’t think you pursue an NIH grant for a dead duck. And it
does seems to have come down to the fact that RE no longer wanted to pursue the work, and he was the expert,

as for “too good to be true “– I completely agree. All the more reason for replication,

 

You've expressed my thoughts perfectly there Sid.

 

Here is some background on Professor Michael Hughes, one of the P.I.'s at Surrey University on the ME Research UK and ME Association funded study to develop a diagnostic biomarker.
Source - https://www.surrey.ac.uk/people/michael-hughes

In short they developed a technique to measure the electrical properties of cells quickly and can differentiate the cells by their electrical properties.

They developed a disposable chip to do the high throughput measurements and it has been commercialized or is in the process of being. Company and product info can be found here - https://deparator.com/

I thought the mention of detecting cell death was interesting.

Several researchers have reported that ME/CFS PMBC's die quicker than healthy cells. I think the Morten Group mentioned it in a report to the ME Association (perhaps Myhill replication work?) and @DMissa and colleagues reported it in their Lymphoblast mitochondrial analysis papers.
One of the theories discussed about the nanoneedle test was perhaps the salt stress was causing cells to die quicker.

Edit to add : Dr Hughes is now at Khalifa University in the United Arab Emirates and visiting professor at Surrey.
https://www.linkedin.com/in/michael-pycraft-hughes-3a77945/?originalSubdomain=ae
So who is leading the day to day work of the ME/CFS salt stress study as Dr Labeed is also in the UAE?

 

There is a video and written description of the DEParator cell separator here
https://deparator.com/elementor-204/

 

I thought their papers on apoptosis could be interesting in relation to the salt stress test. Here is one of them where they use the detection method to look at apoptosis with relation to drug discovery in cancer.
Rapid assessment of early biophysical changes in K562 cells during apoptosis determined using dielectrophoresis
Sue Chin,1 Michael P Hughes,1 Helen M Coley,2 and Fatima H Labeed1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426800/

Here are all the papers listed on the DEParator company website.
https://deparator.com/elementor-321

 

The Surrey University page for Dr Labeed is here:
https://www.surrey.ac.uk/people/fatima-labeed

In the research interests section she mentions developing drug assays, being able to do rapid apoptosis measurement, and cytoplasmic resistance measurement.

Edit to add that Dr Labeed holds a visiting position at the University of California Irvine and has collaborators there. That is where Dr Rahim Esfandyar-Pour works.

Edit 2 : Dr Labeed is now working at the United Arab Emirates University and is now a visiting professor at Surrey according to LinkedIn
https://www.linkedin.com/in/fatima-labeed-phd-0b11b65b/?originalSubdomain=ae
and also this lab page (hosted by wixsite???)
https://yelluk.wixsite.com/my-site-1925/About

 

Some info on the DEP device used for electrical measurement
Source : High-throughput, low-loss, low-cost, and label-free cell separation using electrophysiology-activated cell enrichment
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422786/

(A). Photograph of the DEP separation chip. The chip size is 30 mm × 20 mm. (Inset) Red section shows a close-up of the chip, showing the electrodes along the inside of the wells. The section of the chip in the image is ~5 mm square.


(B) Schematic of the chip, showing the three modes of DEP behavior. Cells flow from top to bottom through the wells; in the left well, cells can be seen experiencing positive DEP, are attracted to the electrodes, and held; in the center well, cells experience negative DEP, are repelled into the center of the well, and pass through. In the third well, cells experience no DEP force. In reality, cells of the same type will experience the same mode of behavior in all wells on the chip, but two different cell populations can exhibit behaviors different from each other. If one subpopulation experiences positive DEP and the others exhibit negative or neutral behavior, they can be separated.


(C) The chip is loaded into a fluidic cartridge comprising two parts; an upper part B contains both housing and plunger, whereas a lower part A collects the cell solution. The chip fits between the two, sealed on both sides by O rings, and is clamped together by three Allen bolts.

 

Just been reading about the new UK study in the ME Research UK newsletter, and my question, from the back seat of the car, is, 'Are we nearly there yet?' That is, do we have a ballpark idea of when to expect results?

 

Always 20 years in the future, as with commercial fusion?

 

Ultimately, maybe, but I was thinking more of when the study's analysis would be reported!

 

https://meassociation.org.uk/2024/0...-properties-of-blood-from-people-with-me-cfs/

Professor Robert Dorey and colleagues update on investigating the electrical properties of blood from people with ME/CFS
July 2, 2024

This jointly funded project by ME Research UK and the ME Association, Prof. Robert Dorey and colleagues at the University of Surrey and London School of Hygiene and Tropical Medicine are currently investigating the electrical properties of blood from people with ME/CFS.

The day-to-day running of the project is being carried out by Dr Krista Clarke, and she and the team have made a good start, recently updating the funding charities on their progress.

Previous research from Prof. Ron Davis showed a difference between people with ME/CFS and control subjects in the electrical impedance of their white blood cells. This indicates an alteration in the resistance of the cells to an electric current, which (while the biological implications are not yet clear) could represent a diagnostic marker for the disease.

Using blood samples from the UK ME/CFS Biobank, Prof. Dorey and team are exploring this further using improved techniques in a larger cohort of patients, including those with mild/moderate and severe ME/CFS.

They have received more than 100 blood samples from the UK ME/CFS Biobank, and, so far, 42 of these have been analysed for their electrical properties. These include samples from those with mild/moderate and severe ME/CFS, patients with multiple sclerosis, and healthy control subjects.

Findings from these groups will ultimately be compared, with the aim of understanding more about the mechanisms involved, and potentially developing an electrical biomarker for ME/CFS.

 

Krista's PhD thesis, embargoed until July 2025
https://www.s4me.info/threads/chara...alth-and-disease-on-me-cfs-2024-clarke.39168/

 

Medscape: Long COVID & Chronic Fatigue: The Similarities are Uncanny

"Using blood samples from the UKMEB, the researchers are now investigating this potential biomarker with improved techniques and a larger patient cohort, including those with mild/ moderate and severe forms of ME/CFS. So far, they have received more than 100 blood samples and have analysed the electrical properties of 42.

'Based on the results we have so far, we are very close to having a biomarker for diagnosis. Our results so far show a high degree of accuracy and are able to distinguish between ME/CFS and other diseases,' said Labeed."