List of diseases with a known mechanism but no cure/treatment

Robert Phair believes it could be a type of a metabolic trap. Apparently this hypothesis has not been falsified. Maybe immune dysfunction caused the metabolic trap but now it’s essentially a biochemistry issue—something like that.

 

I'm half wondering if the problem might be that we've looked everywhere except under the streetlight!

 

Are there any discussions here about it? I’m wonder how they’ve tried to falsify it.

 

Oh right yeah I guess that isn't immune mediated in the same sense.

Although to be fair that lot are if anything overly optimistic about finding a drug.

 

Or in our pockets!

 

From my perspective the problem with the metabolic trap idea is the disease memory problem.
A metastable feedback system that can flip into a 'trap' phase is a neat idea but I find it hard to explain the fluctuations in ME/CFS, with PEM and so on, purely on the basis of a simple metabolic loop. The loop would need to kick in and then kick out and then in again.

Which seems to mean that you actually need another hypothesis to explain the kicking in and out and the trap is just an end product - not an explanation at all and so not falsifiable nor verifiable.

The nice thing about immunity is that it is constantly kicking in and out and we know some of the ways it does that.

If the metabolic trap led back through some sort of immune signalling that could work. I am just inherently sceptical about any theory that focuses on metabolism and energy in ME/CFS because although energy is the first thing that comes to mind in the context of fatigue it doesn't seem t explain all the other symptoms.

 

I think the lists that were provided were meant to highlight some examples to get us thinking not some kind of comprehensive work.

Also I don’t think jay meant abandoning mechanistic work in favor of trialing treatments, just that treatment trials even without an established mechanism shouldn’t be discounted. I think that this path has about as much chance at getting us answers and progress as mechanistic studies

 

One objection to this approach is that we have a limited amount of resources and drug trials are expensive as heck.

 

Knowing the underlying mechanism helps, obviously. But the list demonstrates that it's not a guarantee for the cure. More importantly, neither is not knowing the mechanism a guarantee that no cure is possible. The way things going, we may have to wait another 40 years if we waited for the discovery of the mechanism. I think it's prudent to jump into the trials for repurposed chemicals, and other possible treatments, with both feet.

 

One way to get around that, I think, is off-label drugs. Make drugs available to patients to try as long as they are safe enough, accumulate anecdotes and then trial promising ones.

 

That has already happens. There are plenty of anecdotes but nothing that seems particularly promising. For all we know a drug that works for ME/CFS might be dangerous and or specialized to the point that no one would chose to test it.

 

And screw the patients out of tens of thousands of dollars. As Eddie says bin there done that and held up research progress for decades messing about with things that do no good and may well do harm.

And talking of bin there done that ... I tried one novel drug in my career. And it worked. Because I had good reason to think it would ...

 

We know that people with ME/CFS can experience substantial placebo effects based on the trials by Fluge and Mella. So I don’t see anecdotes as a viable method for identifying possible treatments.

 

I agree. You really need to do what Fluge did - pick up on what seem to be coincidental improvements when drugs are us

 

A single anecdote, no. But many about the same treatment could mean a possibility.

 

Maybe they could finance it as part of investigation for target compounds, funded by RECOVER or something.

It's been-there-done-that for only a handful of candidates. There are thousands of compounds out there that hasn't been tried. There are works going on to identify useful side effects with pharma AI for difficult diseases and me/cfs should be one of the target.

 

Or that enough people have tried it in the same time period as a natural positive fluctuation of their illness.

Or that people report that it works because they want it to work.

We barely have enough funds to cover basic research. Some researchers even have to ask for donations or work in their spare time.

Randomly testing drugs is like playing the lottery to get rich instead of investing over time. It usually doesn’t pay off and a negative result tells us very little about what we have to do instead (or nothing at all).

We have no idea about how ME/CFS works, so we don’t have anything to check the drugs against yet. This approach will have to wait until we have more to go on.

I get why you want to test different treatments. All of us wants a treatment as soon as possible. But I’m not convinced that pouring any amount or money into drug trials at the current stage will take us towards a treatment quicker than if we prioritise basic research first.

The only exception would be if we notice that someone with ME/CFS improves drastically by a treatment that was prescribed for another reason, like what Fluge and Mella found. But even then, there are plenty of confounding variables that could produce false positives so to speak.

 

I agree. It offers some hope. A few on here with success from antifungals, modafinil has helped a few but not me. No one was bankrupted a few helped. Better appreciated if we approach pWME as a varied cohort. Glad to say a decade of calf pain away after a day on nystatin. Placebo? Mechanism please.
Was it ME anyway - no certainty. I nevertheless appreciate the have ago doctors. Better than sore, sore ,sore.

 

Yep. And people have wasted quite enough money trying it with food supplements. Some made themselves worse; they believed there was a real effect, and pushed until they crashed horribly. That would probably get worse with drugs because it's even easier to fool yourself.

I've had long lasting remissions and short-term improvements due to viral infections. If that kind of shift is anything to go on, there'll be little doubt when we find something that really works.

It's not an improvement in some of the symptoms, it's a radical change in all of them. The lifting of burdens you'd no idea you were carrying until they disappeared. If the drug combination was already in use, we'd probably have found it.

 

That’s a very important ethical consideration!