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

poetinsf said:
There are thousands of compounds out there that hasn't been tried.
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Thousands? More like tens of millions.
What about alcoholic extract of old banana skin?
Or sonicated brick dust?
Or gamma-ethyl, 4-keto, 6-hydroxy-analinamide-tetra-sulphate?
Or 5-hydroxy for that matter.

The reality is that things only get tried because some numpty has a bee in their bonnet about it solving this or that putative pathomechanism and up to now suggested look pretty harebrained, like blocking checkpoint inhibitors or whatever.
 
Utsikt said:
Randomly testing drugs is like playing the lottery to get rich instead of investing over time.
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It doesn't need to be rare, expensive, risky drugs. Two of my most effective treatments (cumin and iodine) were already in my kitchen. They haven't had the same effects on anyone else, but they were very effective for my ME. I wouldn't be surprised if there are a significant number of people who developed ME but effectively treated or cured it with common foodstuffs or drugs, and never realized that they had ME (just feeling under the weather, maybe a bug). There might be some relatively common foodstuff or herbal remedy that has helped people, but we don't know about it because they didn't know it was valuable information for the ME community.

I agree that investing in expensive drug testing is a poor choice. Inexpensive testing of common herbs&spices or other such things might be a reasonable investment. A campaign to request PWME to report possible treatments that worked for them wouldn't be expensive, and might turn up something useful. Reports of negative responses, such as "Turmeric made me crash for 6 months." might be helpful too.
 
Creekside said:
It doesn't need to be rare, expensive, risky drugs. Two of my most effective treatments (cumin and iodine) were already in my kitchen. They haven't had the same effects on anyone else, but they were very effective for my ME. I wouldn't be surprised if there are a significant number of people who developed ME but effectively treated or cured it with common foodstuffs or drugs, and never realized that they had ME (just feeling under the weather, maybe a bug). There might be some relatively common foodstuff or herbal remedy that has helped people, but we don't know about it because they didn't know it was valuable information for the ME community.

I agree that investing in expensive drug testing is a poor choice. Inexpensive testing of common herbs&spices or other such things might be a reasonable investment. A campaign to request PWME to report possible treatments that worked for them wouldn't be expensive, and might turn up something useful. Reports of negative responses, such as "Turmeric made me crash for 6 months." might be helpful too.
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If common herbs & spices were the cure to ME/CFS it wouldn't exist anymore (I suspect you'd also expect prevalence differences in countries that put iodine into salt vs those that don't, maybe you'd even expect prevalence differences in people that had a thyroidectomy vs those that didn't etc). A campaign to request PWME to report what they improved has occured on different occasions and is likely to just be a report of what is currently trending on social media and unlikely to be of any relevance. In fact such a report would only show that cumin and iodine are not treatments of ME/CFS. We have already seen numerous such studies in the case of Long-Covid, none of which have turned up something useful.
 
Utsikt said:
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.
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Those are possibilities too. We should let a trial, like the one for glucosamine for cartilage, settle the question rather than dismissing them out of hands. As long as they are promising.

We barely have enough funds to cover basic research. Some researchers even have to ask for donations or work in their spare time.
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RECOVER wasted colossal amount of money doing the "basic research". All they did was reinvent the wheel. We might have something useful by now if they spent some on figuring out potentially useful repurposed drugs and trialed promising ones.

Randomly testing drugs is like playing the lottery to get rich instead of investing over time.
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Individually, that is true. I'm thinking there could be a systematic way to do this collectively. If AI can speed up the process with pennies, that would be great. Or there might be a statistical Monte Carlo method to do this effectively and sort through thousands to find a needle in haystack.

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.
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This is something I've been saying for a while: white box is not the only way to figure out things. You can do that to some degree even with black box. The way things going, I don't think any of us will be alive to see the solution if we relied solely on the white box approach.
 
Creekside said:
It doesn't need to be rare, expensive, risky drugs. Two of my most effective treatments (cumin and iodine) were already in my kitchen.
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https://www.s4me.info/threads/malic-acid-supplement-sumac.42716/page-4#post-594525
for what it’s worth, I did also discover a huge boost from a kitchen spice (sumac), just one that tends to be used sparingly in cooking so I never ingested a larger amount before.

Although multiple people have reported to me that they got similar huge boosts of energy and pain relief (doing their best to account for placebo effects), others have reported no effect.

It’s entirely possible that pwME end up with the same or similar downstream pathology from different exact mechanisms, so some random thing that works for a subset wont work in others.

I think there is some valuable information to be learned from random reports like this, even if it is only a subset. But in order to be maximally effective, it would probably need to be paired with in-depth information that could help sort out responders from non-responders. Needless to say, easier said than done.

note: in my case, I did arrive to the kitchen spice based on putting together some puzzle pieces in the literature.
 
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There’s also a platform called Eureka that tries to bring together people’s reports for things that worked for them for various illnesses. I was on it briefly a little over a year ago.

Edit: nevermind, I just checked and the project appears to have disappeared off the face of the earth. Shame, since it was a useful platform.
 
poetinsf said:
RECOVER wasted colossal amount of money doing the "basic research". All they did was reinvent the wheel. We might have something useful by now if they spent some on figuring out potentially useful repurposed drugs and trialed promising ones.
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As far as I can gather RECOVER wasted money on dumb research. 95% of research is dumb so not surprising. If they had set up a GWAS like DecodeME in late 2020 on 100,000 people we would have the answers now for a fraction the cost.

How do you figure out potentially useful repurposed drugs if you have no idea what to figure? What magic wand were they supposed to wave or what oracle consult? Across the population of people with Long Covid - say 5 million - there would be people trying almost any known prescribed drug so you might as well wait for serendipity. That has been quite useful over the years. Several drugs have com into use because they were by chance found to help. Phenylbutazone was originally used as a solvent rather than drug. Chloroquine was found useful in RA when people took antimalarials. Gold was found useful because it had been used for TB. Amantadine for Parkinson's was originally an antiviral I think. Viagra was being trialled for something else. Unless you are talking about things like aspirin reducing stroke risk over decades when most drugs work usefully it isn't difficult to notice the benefit. And it seems that kitchen spices do better than the groaning shelves full of prescriptions waiting to be picked up in my local pharmacy, just for one high street's residents.
 
poetinsf said:
We should let a trial, like the one for glucosamine for cartilage, settle the question rather than dismissing them out of hands. As long as they are promising.
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If something is dismissed by people on the forum it’s most likely because there isn’t enough evidence to warrant a trial.
poetinsf said:
RECOVER wasted colossal amount of money doing the "basic research". All they did was reinvent the wheel. We might have something useful by now if they spent some on figuring out potentially useful repurposed drugs and trialed promising ones.
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We most likely wouldn’t because we have no idea about what we’re trying to do with the treatments.

You’re essentially asking a mechanic to try and fix a car by going to a general hardware store and picking an item randomly.
poetinsf said:
Individually, that is true. I'm thinking there could be a systematic way to do this collectively. If AI can speed up the process with pennies, that would be great. Or there might be a statistical Monte Carlo method to do this effectively and sort through thousands to find a needle in haystack.
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Again, we do not know what we are lookikg for. AI isn’t some magic wand you can wave. It has to have something to go on.
poetinsf said:
This is something I've been saying for a while: white box is not the only way to figure out things. You can do that to some degree even with black box. The way things going, I don't think any of us will be alive to see the solution if we relied solely on the white box approach.
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It doesn’t seem like you’re considering how many possibilities the black box contains.

I think the chance is even lower if we take your black box approach. You pretty much guarantee it.
 
Jonathan Edwards said:
As far as I can gather RECOVER wasted money on dumb research. 95% of research is dumb so not surprising. If they had set up a GWAS like DecodeME in late 2020 on 100,000 people we would have the answers now for a fraction the cost.
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Have they still not done a GWAS on Long Covid? Will DecodeME be the only GWAS to include PwLC?

...you might as well wait for serendipity. That has been quite useful over the years. Several drugs have com into use because they were by chance found to help. Phenylbutazone was originally used as a solvent rather than drug. Chloroquine was found useful in RA when people took antimalarials. Gold was found useful because it had been used for TB. Amantadine for Parkinson's was originally an antiviral I think. Viagra was being trialled for something else. Unless you are talking about things like aspirin reducing stroke risk over decades when most drugs work usefully it isn't difficult to notice the benefit.
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We've discussed this before, how to properly interpret and take advantage of individual PwME trying things that they're taking outside of a clinical trial. I think we concluded that the thing to do was to then proceed immediately to a clinical trial but we never solved the problem of how to identify the front-runners in any useful way. There are so many people trying so many things and a certain amount of variability in people's ME/CFS over time that there's such a lot of noise in the data.

But there are people whose ME/CFS stays dead-flat stable for years (I'm one) and people who seem to find something that works for them in an N=1 on/off/on kind way. Maybe that's where to look for a clearer signal.
 
Jonathan Edwards said:
How do you figure out potentially useful repurposed drugs if you have no idea what to figure? ...Across the population of people with Long Covid - say 5 million - there would be people trying almost any known prescribed drug so you might as well wait for serendipity. That has been quite useful over the years.
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This raises the question of why serendipity hasn't yet coughed up a drug for ME/CFS, given that there are presumably tens of millions of us worldwide and we've been around much longer than PwLC. Drs Fluge and Mella noticed rituximab and did a proper trial but what about all the other drugs? Are clinicians just not paying attention?

From another thread:

Jonathan Edwards said:
IL-17 is a T cell derived cytokine that probably does lots of things. It seems to be involved in seronegative spondarthropathies which for me are the closest analogy I can think for what might be going on in ME/CF immunology. I don't have any more specific justification than that but at least it is about as logical as using rituximab if you think antibodies cells are involved.

I mentioned it Lipkin because he has given a presentation that mentioned IL-17 levels in ME/CFS. I seem to remember that Mady Hornig found a difference. I think the justification was moot but I would probably put it ahead of a lot of other things. IL-17 blockers have been used in other conditions and seem fairly safe.
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I wondered if we would expect serendipitous observations of IL-17 helping PwME if you're right about it but I can't find on Google that IL-17 is a drug or is used for any disease.
 
Sasha said:
This raises the question of why serendipity hasn't yet coughed up a drug for ME/CFS,
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Presumably because there isn't one out there. By and large drugs that are really worth having and safe (phenylbutazone, gold and chloroquine are not) are synthesised on purpose after careful sorting of options once a lead is discovered. There may be twenty out of a thousand diseases for which we have a viable serendipitous agent. So the odds are not that good. But serendipity is likely to be at least as efficient than just going through an alphabetical list of chemicals already being used.
 
Jonathan Edwards said:
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 ...
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I think it goes without saying that everyone here in favor of doing treatment trials without already having an established mechanism are not in favor of just trying things randomly or based on a hunch with little evidence. For sure we would want to have preliminary evidence pointing in a direction where, as you said, would give us good reason to think it could work.
 
poetinsf said:
Why dismiss them out of hand? If many people report blood-letting or homeopathy improving their condition, then we should do a trial.
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Because individuals saying they work isn't enough to make the case for a trial. You need more, including basic scientific plausibility and an assessment of the likely reliability of reports.

Blood letting is still used on my relatives, as it happens (it's the most reliable way to reduce iron load in genetic haemochromatosis), but it wouldn't pass the plausibility test for many other things. Painting your toenails with parsnip juice might work for ME/CFS, but I can't imagine anybody volunteering to fill in the paperwork!
 
Sasha said:
Will DecodeME be the only GWAS to include PwLC?
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No, as DecodeME is only looking at people with ME/CFS. That does include a small cohort of people who report developing it following a Covid infection and who match the same selection criteria as the rest of our cohort, but that isn't the same as saying that we have a cohort of pwLC.
 
Sasha said:
Have they still not done a GWAS on Long Covid?
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There have been several GWAS on LC across the globe, some of which have been discussed on this forum. The problem, as always, has been the heterogeneity of LC.

A genetic study looking at phenotyped LC patients more would have been a very fruitful attempt but RECOVER wasted almost all their money on meaningless nonsense. A while ago a link was posted that RECOVER wanted to run a genetic study, but with RECOVER you never know if or when it will happen or what the cohort of patients even consists of. Good luck finding a genetic link between stroke, PICS, headaches, smoking, anosmia, obesity, OI and ME/CFS...
 
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