How to best move the understanding of ME/CFS forward (and the forum's role in that)

[V.R.T.]

I realise that. But I say what I do having spent a career in developing treatments from basic animal lab work to actually making up the infusions for my patients. I was sufficiently committed to getting a result that meant something for patients to spend $15,000 of my own cash on buying a drug to give patients because not even the drug company wanted to pay for it. It worked, but during the process of testing it a few people died. On balance I think it was definitely worthwhile (as did the licensing bodies) but there was a very strong lead for thinking it would work (at least I thought so) and I don't see that of any drugs for ME/CFS at present. In that situation I would put the cost/benefit analysis as something like 9 points against to 1 point for. Drugs are toxic. Tens of thousands of people have died from using anti-inflammatory drugs we used to think were safe to hand out for trivial pains.

On the other hand making a drug to order now is so easy that I would be optimistic that once we have an idea what it is we want to put right a drug could be made available very quickly. I strongly suspect that there is some sort of signalling problem and signals are particularly easy targets. But we don't know what they are.

I have overgeneralised a bit. I have recently reviewed two grants for other European countries, one of which looked quite good and may well be funded. There are some things worth following, I agree. Complement might be, antibodies to flagellae might be, pathway analysis proteomics might be, amino acid metabolism might be. TGF beta might be. But the methodology has to be good enough to produce a solid answer and that has often not been the case.

I do agree with a lot of what you say and I sympathise with your concern about safety for trial participants. And I'm sorry to hear about the patients that died.

As you say, drugs are toxic and can have adverse effects. But the adverse effects of leaving people to rot when there are things that could be trialled now must be considered too. I'm not going to lecture you on what it's like to be at the mercy of a hostile medical/benefits system etc because I'm sure you're aware.
But in my opinion that, and the nature of PEM, make this a much more urgent issue and tilt the risk/benefit axis somewhat.

If some of these long covid drugs have a positive signal in phase 2 against PEM/ fatigue, surely you would support an ME trial? Or if the drug the Norwegians are doing a pilot study on shows promise, for example?

And stuff like LDN and Mestinon needs to be properly tried, because people are using them anyway. But the OMF are doing that so perhaps a moot point.

In terms of the interesting papers you mention, surely if these findings might be worth pursuing then they are worth pursuing, because how else can they be verified or proven false? We have a lot of interesting studies in ME/CFS that no one has tried to replicate because of funding issues.

Could a drug to order really be made available so quickly? I was under the impression a new drug would take at least a decade to progresss through trials and reach patients. And that new drugs fail all the time. If what you say is true there is more hope than I thought.

 

[Jonathan Edwards]

In terms of the interesting papers you mention, surely if these findings might be worth pursuing then they are worth pursuing, because how else can they be verified or proven false? We have a lot of interesting studies in ME/CFS that no one has tried to replicate because of funding issues.

Yes, I am not wanting to argue that there is nothing worth doing. There are some things to follow up but the people concerned are likely to be doing that I=f they really believe their own results.

My main point was simply that I don't think forum members should be criticised of responding their time discussing science rather than raising funds. My guess is that if raising big funds for ME/CFS was really a practical option someone would have succeeded by now. And certainly not many people have any idea how todo it. On the other hand I see the discussions as hugely productive. People see different sides to an issue when they have to justify their position in debate.

Certainly for me, the discussions here are absolutely essential to the knowledge I have gained which I feed back in terms of reviewing the grant applications that do come through.

If some of these long covid drugs have a positive signal in phase 2 against PEM/ fatigue, surely you would support an ME trial? Or if the drug the Norwegians are doing a pilot study on shows promise, for example?

If anything gives a reliable positive signal then yes, but I am not very optimistic that anything being studied so far is going to provide a major breakthrough.

 

[V.R.T.]

My main point was simply that I don't think forum members should be criticised of responding their time discussing science rather than raising funds.

Certainly for me, the discussions here are absolutely essential to the knowledge I have gained which I feed back in terms of reviewing the grant applications that do come through.

We are in agreement there!

 

[Kitty]

But the adverse effects of leaving people to rot when there are things that could be trialled now must be considered too ... But in my opinion that, and the nature of PEM, make this a much more urgent issue and tilt the risk/benefit axis somewhat.

The axis may be tilted for some of us, but it has to be for the doctors and the ethics board too.

They see people with a puzzling but potentially reversible condition, who are (apart from ME/CFS) fairly healthy. It must be difficult to justify use of a risky drug whose benefits are uncertain even when the misery of living with ME is taken into account. Looking a year or two ahead, it's far more likely that we'll have a treatment for ME than one for organ damage caused by a cascade of adverse drug effects.

[Edited last sentence word order]

 

[V.R.T.]

The axis may be tilted for some of us, but it has to be for the doctors and the ethics board too.

They see people with a puzzling but potentially reversible condition, who are (apart from ME/CFS) fairly healthy. It must be difficult to justify use of a risky drug whose benefits are uncertain even when the misery of living with ME is taken into account. Looking a or two year ahead, it's far more likely that we'll have a treatment for ME than one for organ damage caused by a cascade of adverse drug effects.

I understand. I am certainly not advocating for gung ho administration of anything and everything.

I am afraid im out of spoons so cant reply further

 

[Amw66]

Einstein's early work was all based on reinterpretations of the empirical work of others.

He was inspired by Hilbert's approach (in mathematics) to re-frame all of the important theoretical findings in physics and, well, succeeded in doing something similar...

The key point was 'standing on the shoulders of giants', something that most of the LongCOVID researchers failed to do, when they made their NIH cash grab. It's all new they said. If only they took the time to learn that it was not.




I am not the only one, but I have quite a list of research proposal ideas (and some idea of what techniques to use) across the spectrum, from mathematical modelling, to neuroscience, to exercise physiology, to qualitative research.

Such as theoretical modelling of the relationship between muscular blood flow and motor unit recruitment and fatigubility (and their relationship with the anaerobic threshold), further examining the neuroscience of afferent feedback from muscles and using specific new techniques in neuroscience, validating some alternatives (EEG, EMG, TMS) to maximal cardiopulmonary tests in demonstrating 2-day fatigubility and also providing an objective basis for which we could test pharmacological interventions.

I think the emphasis should be on trying to build the dart board first, rather than just throwing darts and hoping for the best.

Oh and a robust way of developing new composite (PROMs & objective measures) outcome measures that starts with qualitative research, with active participation of patients to see what doesn't work in prior scales, to see what most relevant, to develop a scale and then go back to the qualitative stage in the context of a clinical trial to ask patients whether the questions are relevant and how easily they think the scale (and other prior scales) could be biased. Doing online surveys alone is not good enough.

Rather than going oh, CFS is defined by fatigue, let's throw an bunch of 'fatigy' questions together (if anyone asks, we'll say they were generated by various experts), performing some correlation statistics (without understanding that social context biases can create false correlation) to make sure there are no odd-one-out questions, giving it to 100 consecutive attenders to a general practice and then pretending it's reliable and valid in different contexts, such as the primary outcome in clinical trials. And pretending it will have good face validity because a similar scale made by a friend was tested for face validty in a different study. She'll be right mate, I'm sure patients will love it.



Neither will researchers if they keep kicking the can down the road rather than actually doing ground breaking work. There are a few diamonds in the rough, but there aren't enough people to cause a critical mass. This is why they need to be open to patient-researchers to keep them on their toes, always asking 'can you do better'.

So much this . Thanks for putting it so eloquently

 

[Sid]

It worked, but during the process of testing it a few people died.

Of infection?

 

[Jonathan Edwards]

Of infection?

Probably more of sterile pneumonitis. I am not sue this has ever been adequately sorted out. Cell depleting monoclonals can produce serious acute events.

 

[FMMM1]

Re the 100 Million, it's entirely possible to get that kind of money working in less than 24 - 36 months

Karl Morten attempted (crowdfund) to raise money to fund ME/CFS research but didn't succeed.

 

[FMMM1]

For a problem like ME/CFS you have to start with medical academics having some understanding of what the illness is actually like. The real problem I see is that ME/CFS has no clinical service base that would allow medics to learn what it is they want to study. Scientists only get involved when asked by a medic to solve a clinical problem with lab work. If nobody knows where to start then the scientists are not going to see the point.

Thanks - interesting insight.
@ME/CFS Skeptic

 

[MelbME]

I think a focus on understanding PEM is the best funding direction.

I think you need to know when patients are close to it. Knowing that accurately would be a key test to timing different intervention strategies. It's critical.

Detailed analysis of patients going through it and recovering back up close to baseline. Many different ways this could be done.

 

[Yann04]

I think a focus on understanding PEM is the best funding direction.

I think you need to know when patients are close to it. Knowing that accurately would be a key test to timing different intervention strategies. It's critical.

Detailed analysis of patients going through it and recovering back up close to baseline. Many different ways this could be done.

That’s been my intuition too. PEM is a major disease process and mechanism in itself. It is what makes ME stand out as a different clinical entity. I really think the large majority of research funding should go into understanding it.

 

[forestglip]

Isn't there an issue of scientists avoiding even entering the field because of lack of research funds? Where they don't want to devote their life to something where every grant will be rejected?

Quote from an interview with a researcher, Tina Katsaros, in Breakthrough magazine, Autumn 2024:

"Where do you see yourself five years after completing your PhD?
I would love to stay in ME/CFS research, but funding can be challenging to come across – which is why it’s so amazing that there are organisations like ME Research UK that help to fund the research. Ideally, five years after my PhD, I will be doing a post-doc somewhere that allows me to continue ME/CFS research, and, who knows, maybe even a fellowship."