What research do you want to see? (study ideas)

Something I'd like to see is for one of the organisations to coordinate things better and fund some small projects on top of existing projects where it is sensible to follow-up on existing results.

Precision Life seems like a perfect example, but there is far more potential.

For example Rob Wüst doesn't seem to have the means to look at WASF3 in his Long-Covid and ME/CFS samples. However, all the hard work has already been done (patient selection, muscle biopsies, CPETs etc). All one would have to do is run an additional WASF3 analysis. For all I care one could even organize a travel grant for Hwang, pay for his flights and a 4 week hotel stay in Amsterdam and let him run all the samples. We'd have the results by the end of the year at costs below 100 000$. Instead we'll have to wait and see, possibly somewhere along the line there'll be negative results we never hear about and everything disappears into the abyss again.

Have there been other interesting results from the past that should be followed up on even if it just to get definite negative answers, can these be combined with existing projects?

 

Public one here, What research do you want to see?

 

I'd be interested in a very focused look into acquired immune tolerance and how it may relate to pwME.

I'm not quite clear on a few things, not the least of which: If our bodies aren't generating the antibodies they should to whatever agent they should be reacting to, then how do we know that in the first place?

 

It's good to see increasing numbers of studies looking at PEM. I'd love to see some research on what happens *before* PEM, what chemical state the body gets into when it's responding to unusual demand, which triggers or cascades into PEM later. What it is that enables us to 'push through' at a higher level of exertion. Is it adrenalin in combination with some other thing or things? And whether it's the same process that lets healthy people 'push through' times of great demand or stress, and what kind of backlash they experience.

There are lots of teachers in my family, so I'm thinking of the classic thing that happens at the end of each school term, where they power through a couple of manic weeks and then spend the first 3 days of the holidays feeling ill with non-specific flu-like symptoms! It's usually assumed that the illness is a viral infection that they've been fighting off until they get a chance to stop and rest. Is that fighting-off-and-then-crashing the same sort of process as pwME exerting themselves and then crashing into PEM, only on a much smaller scale?

 

Test a large number of people for as many common toxins as possible, including things like DDT, Dieldrin, HCBs, PCBs, Mirex, Lindane, Mevin-phos, p-dichlorobenzene, Pentachlorophenol, Carbaryl, Toxaphene, and look for any correlations with symptoms. Not necessarily limited to ME symptoms, it can be a shotgun approach for many chemicals and many conditions. Any promising findings can then be studied more carefully.

The above list of chemicals is from Four Cases of Pesticide Poisoning, Presenting as “ME,” Treated with a Choline and Ascorbic Acid Mixture, a paper from 2000 with four case reports. Each person had been exposed to large amounts of different pesticides and was experiencing an ME-like illness. Blood tests showed different combinations of the above chemicals. After treatment with choline and vitamin C, the levels of the above chemicals were greatly decreased as were their symptoms.

Table showing blood levels of chemicals in the four patients over time:


Most of the above chemicals are organochlorine pesticides. I think most or all of the above chemicals are fat soluble and can persist for a long time in the body, and many or all have been banned in some jurisdictions due to health effects. I think all four people had no idea there could be a connection between the chemicals and the symptoms until the doctor suggested it.

One example:

If this person potentially got ME from visiting a hotel in South Korea for two weeks because of chemicals that persisted in his body, how many people that live their whole lives in that area getting constant exposure have similar symptoms that no one has realized might be linked to the pesticides? If in places where they were banned, testing older people may show they still have relatively high levels from before the ban.

Organophosphates, purportedly a safer form of pesticides, have been linked to gulf war illness, psychiatric disorders, and fatigue, and are still used in many places.

I would like to see a study looking at a large number of people (>1000), maybe only older age, some healthy, some with chronic conditions, such as ME, Parkinson's, Alzheimer's, arthritis, asthma, or depression, and test them all for as many chemicals as possible, prioritizing for chemicals that are more affordable to test, that are more commonly used, (or have been commonly used in the past if they persist for a long time), that are most likely to be harmful to health (e.g. chemicals where acute exposure is definitely harmful, or related compounds to these), and where a significant portion of the population is known to have non-zero levels (like microplastics). Analyze the results for any potential correlations to symptoms to then pursue more targeted research on any chemicals showing correlations.

 

Yep—though so many papers come out that it's quite hard to mentally shortlist the potentially promising ones.

I do think the WASF3 finding ought to be pursued, so we know whether it looks like a priority for further investigation or it's an anomaly that can be ruled out.

 

Not just NFL - there are a variety of potential/emerging biomarkers of neuronal and axonal injury such as ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP):

Here's a table with some others, along with descriptions of sources and findings from the TBI literature:

 

I'm not sure if this has been attempted, but if not, I'd like to see someone try to make an in vitro 2-day CPET. It might be possible to extract a few muscle cells from people with ME, stimulate them with electricity to simulate exercise, and see if their responses on day two differ from non-ME.

 

If this hasn’t already been done before. I want a large cohort of people who’ve been diagnosed with ME or “CFS”, them to all go through questionnaires for major diagnostic criteria:
IOM, ICC, CCC, Fukuda, Oxford. And a couple questionnaires that might be good at predicting ME, such as FUNCAP, DePaul PEM questionnaire etc.

Then make all these patients take a 2-day CPET. And find which diagnostic criteria and surveys are best at predicting abnormal results.

 

Test markers of pathogen levels (RNA, antibodies, etc) on both days of a 2-day CPET to test the hypothesis that ME is related to live pathogen persistence and that PEM is an increase in pathogen levels/proliferation, which would explain the delayed symptoms after exertion and the flu-like symptomatology.