Can you say whether the planned GWAS collaboration with Lipkin/Columbia was going to be in ME or LC?
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List of diseases with a known mechanism but no cure/treatment
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Can you say whether the planned GWAS collaboration with Lipkin/Columbia was going to be in ME or LC?
The problem with that is that the true believers will likely reject any trial that doesn't provide positive results, and it doesn't matter how implausible their reason for the trial being flawed.
Looks like you're right, to my own suprise they have all been small. I can only find one larger one (52 000 cases - self identified and recruited via 23andME) with all others being of miniscule size.
I'm unsure how much work is happening in the background. At least it seems that there are/were 7 genetic Long-Covid studies happening in Germany alone (genomLC, BoSCO, long non-coding RNAs in Long-COVID, The role of genetic risk profiles in the development of post-COVID symptoms, Genome-wide association study to identify genetic risk factors for Post-COVID Syndrome, Influence of genetic background in COVID-19- and Long-COVID phenotypes, Is there a connection between the severity of COVID-19 disease, the development of long-COVID syndrome and a specific genetic cell variant in carbon metabolism?).
Given what I had misremembered myself, I think it may be a decent idea to keep an overview of the different genetic work in Long-Covid. I'll make a thread later.
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Andy
Retired committee member
ME/CFS. Grant details can be found here, https://reporter.nih.gov/project-details/10878255
That seems like a worthwhile project in terms of replication. Beyond frustrating that funding has been pulled. I hope that the government sees sense but not holding my breath. Perhaps there are alternative funding sources that could be explored, as discussed in the SequenceME thread?
If we sat on the scientific plausibility, bloodletting or geocentric theory is precisely the kind of things we would end up with. We have things like the relativity, evolution, or even the control of communicable disease spread through water because some people observed and then went out of the way to investigate rather than getting limited by the scientific plausibility de jour.
If many people are reporting that painting the toenails with parsnip improve ME/CFS, there could be something in it even if we don't know what it is yet. Why not investigate rather than dismissing it as implausible, right?
Here is one. I thought there was a large European study, but I don't seem to be able to find it.
Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis | New England Journal of Medicine
And that's what you would do if you had an opaque gadget you don't know anything about. You kick it around, see how it responds, and try some random stuff. You incorporate what you learned and then try the next random stuff, revising your theory about it on every step, till you fix it.
You don't really have to know what it contains. You just need to know how it responds to some (random) inputs to hypothesize about it. If you think about it, we don't really know anything about anything. All we know is how something behaves in certain situations, which translates to predicting how it will respond in some other situations.
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You figure it out by trying it? It ain't no use to sit and wonder why the roof is leaking. Somebody should jump on the roof and start poking around.
Wouldn't it be great if we have one like that for ME/CFS? Why not systematically scour through them all to see if any clicks rather than leaving it to chance?
That would be an incredibly inefficient way to go about it. Given you know nothing about the issue there are literally an infinite number of things that might fix it. If you try something and it doesn't work all that tells you is that you can rule out that one specific thing, assuming you did that one thing correctly. If what you try works to some extent that can tell you something. But that assumes you know enough about the thing to recognize when you actually helped and when it was factors outside of your control that helped.
Wouldn't a significantly better approach be to take apart the gadget looking for clues as to what is wrong. Keep breaking the gadget down into smaller parts and observing these parts until you get to a level at which some understanding exists. Then once you have an understanding of how the gadget works you will know what kinds of stuff might work and don't have to try everything.
Utsikt
Senior Member (Voting Rights)
@poetinsf we’re going in circles here.
I believe your suggested approach is about the most inefficient way of solving a problem that we barely know anything about.
We all want treatments, preferably yesterday. But we have to think long term and go for the approach that on average takes the least amount of time. And that’s trying to figure out the core of the problem.
Your approach has a minuscule chance of succeeding in the short term, and only a slightly better chance long term. But you’re still suggesting to gamble on getting incredibly lucky.
Trying to figure out how ME/CFS works will not be able to get us any solutions short term. That’s difficult to accept when we’re suffering so much.
I believe your suggested approach is about the most inefficient way of solving a problem that we barely know anything about.
We all want treatments, preferably yesterday. But we have to think long term and go for the approach that on average takes the least amount of time. And that’s trying to figure out the core of the problem.
Your approach has a minuscule chance of succeeding in the short term, and only a slightly better chance long term. But you’re still suggesting to gamble on getting incredibly lucky.
Trying to figure out how ME/CFS works will not be able to get us any solutions short term. That’s difficult to accept when we’re suffering so much.
Jonathan Edwards
Senior Member (Voting Rights)
Well that one didn't seem to settle a question since they got no rest but still suggested it might work in a subgroup!!!
Jonathan Edwards
Senior Member (Voting Rights)
Jonathan Edwards
Senior Member (Voting Rights)
Because if you actually tried them in doses adequate to know if they would work and ranges of protocols that you would need to check to know if they worked you would almost certainly kill at least 100 people through adverse reactions.
I get the impression that you have no experience with choosing drugs to try on diseases! I spent my life doing that. I am telling you what I learnt. We had deaths even when we picked things on the basis of some decent rationale.
Andy
Retired committee member
I guess there could be alternative funding sources but that would be down to Columbia to explore.
Whose brain are you offering for this taking apart? Also, human brains don't work very well when you take them apart, so you can't see the malfunctioning bits in operation. Technology for studying brains in operation is advancing, but for a lot of purposes, the brain is still a black box. My engineering background directs me to study this by applying various inputs and seeing what the outputs do.
We simply can't try all existing drugs for their effects on ME. We don't know what dosage would be required to have a noticeable effect, so you'd have to try maximum doses, which is risky, while some drugs have only a narrow range of dosage that is effective. I'm hoping that someone stumbles--through self-experimentation--across something that provides a reliable effect (positive or negative) for a significant number of PWME. Then someone can try to figure out how it's doing what it's doing.
Kitty
Senior Member (Voting Rights)
The same reason you don't try to read the British Library's 13 million books in the hope of finding the one you want. It's not a rational way to go about it.
The analogy was to a gadget. In humans we would have to use imaging or blood samples to see what is going wrong. That can be done while the malfunctioning bits are in operation.
How do you know we have to try maximum doses? There might be some non-linear dose dependent response.
If you think there is a realistic chance that someone will stumble on the correct drug and dose to treat ME/CFS than I understand why you would take this position. But people have already tried the drugs where there is some (questionable) rationale and those that aren't particularly dangerous. There are also plenty of treatments that people have claimed have a reliable effect on ME/CFS. Of the list below do you think we should sink significant resources into running trials on each one?
Attachments
That doesn't work if the problem is hidden deeply inside brain cells. It could be the contents of vesicles that only travel from one part of the cell to another part of the same cell. Blood samples won't reveal that. We may not yet have the technology that would reveal ME's core dysfunction.
The problem there is that you can't rule out a treatment until you do try it at all dosages, including maximum dosage. Add in the possibility of critical cofactors in various dosage. The combinations to completely test a treatment quickly reach improbable numbers. If you say "Well, just test the most likely ones at the most likely dosages.", how do you determine which ones are most likely and what dosage is most likely? That's what has been done for decades, with each researcher deciding what they think is most likely based on their pet theory ... and we've seen the result.
Someone may have already stumbled across a useful treatment, but it's someone in some undeveloped region who tried a local material, but they never heard of ME, so they haven't reported it to anyone who doesn't know about ME.
When I was shopping yesterday, I noticed a package of "Carom seeds (ajwain)", which I'd never encountered before. $1.69 is a cheap gamble, so I bought some. I think it's unlikely to have an effect on my ME, but I would have rated cumin similarly unlikely, yet that proved to be amazing for me.
That's a good counterexample for "test the most likely ones": cumin probably wouldn't have made the list. Neither would 3-5 diiodothyronine. The treatments that someone decided were "most likely" are probably the equivalent of choosing stocks based on which were most popular at the moment, rather than a deep understanding of the businesses.
I completely agree, and I think the problem might be something like that. I would argue that makes it all the more important not to use money on treatment trials without a good justification and instead in developing new research tools.
That's why I don't think testing treatments in this way is likely to be successful. Without a good idea of where to look you have to try all treatments at a range of doses to ensure you haven't missed it.
I am glad you found something that works for you. But what is your criteria for deciding what to spend money on and test? What makes cumin more likely to work than any other of the drugs above?