Suppose you have €5-10 million for ME/CFS research, what would you spend it on?

[Re my comment about GWAS and the 'role' of IL-10 in rheumatoid arthritis and other autoimmune diseases]

Oh dear, I can clearly no longer rely on my memory to accurately recall stuff like this! Thanks for pointing out my error.

I should have referrd more broadly to the iL-23 pathway, where GWAS have played a leading role in implicating them in several autoimmune diseases including RA and psoriasis. There are drugs based on IL-23 such as ustekinumab for the latter, and I think some of these drugs have also been applied to other autoimmune diseases (though I don't have the screen time capacity right now to follow up on this).

 

@Hutan

After some thought on this, I agree that many so-called ME/CFS doctors lead patients to assume they will be successfully treated.

But there are exceptions.

At first, just regarding a couple of more specifically ME focused mainstream physicians I consulted, I would say my experience was 50/50. Both tecommended DIY treatments. One of these doctors did not lead me to believe I would have successful treatments.

However, digging through my memory bank, I've seen a number of other MDs who practiced both alternative and mainstream medicine. They seemed fairly confident I would greatly improve/recover/have successful treatments. They were not reported ME specialists, but treated complex, "mystery" illnesses.

Out of the many physicians I've seen re ME, only one has been knowledgeable enough about this disease to basically say, "I don't know".

 

The Jason 1999 community prevalence study was based on just 32 CFS cases: 0.42% prevalence with an overall 95% confidence range of 0.29%-0.56%. The confidence intervals for male and female prevalence separately will be even wider than this so that the sex ratio can tell us nothing reliable. I haven't looked at the 2020 prevalence study, but I'm guessing the situation is similar there.

 

Yea you can see from Simon's post above, re the migraine study [identifying the CGRP pathway], that an ME/CFS GWAS was a good idea - Jonathan identified that as a promising research area i.e. in the MRC group looking for research areas.
Anything re actimetry e.g. could it come through the current UK Government groups on ME/CFS?

 

One thing that comes to mind, re the migraine study, is that it had (?) a much more homogeneous population than ME/CFS (correct?). E.g. 50% of people benefit from a drug targeting that [CGRP] pathway - so likely to give a strong signal in a GWAS study. I'm hoping that maybe GWAS can still identify pathways i.e. even if the the population is more heterogenous. Other thing might be bigger GWAS studies/filtering to get a more homogenous population - but how to filter - actimetry?

 

Yea but check out Simons comments re migraine GWAS study - gene identified is a recognised successful drug target (50% of patient population). So, as Simon highlights, if you nothing about migraine then this GWAS study would highlight the pathway/potential drug targets.
OK I'm worried we may have a more heterogeneous (ME/CFS) population and therefore need bigger GWAS studies. Potentially bigger subgroups can be identifies, with targets for drugs, and then the remainder re-analysed --- bit like fractionating beach gravel with different sized sieves.

Not sure I'm making sense!

Yes others want drug trials --- as you suggest.

 

Posts moved from this thread:
Experience with LDN?

IVIg?

 

I'm wondering if you've any suggestions i.e. trials you'd like to see?

 

I know this wasn't addressed to me, but when I think about it, all I get is a question in return. If there is a really effective disease modifying drug already out there, shouldn't we have stumbled on it by now? ME is common enough that patients must surely have been treated for other conditions with many of the major drug classes, and (at least in the West) substantial numbers have been networked via the internet now for a couple of decades at least. The word ought to get out.

Yes, there have been a few instances where it appears something works, and there are a couple of candidates like LDN and Abilify that perhaps ought to be trialled, but really, the silence is deafening.

 

Yea and I shouldn't jump to try to conceal the truth of your comment but ---

Jonathan highlighted that TPPP* (turned up in a small GWAS study) would fit the bill i.e. you'd expect it to look like ME/CFS. If e.g. it was TPPP then there may be drugs available to try (drugs approved for sleep regulation?) or e.g. the recent successful trial on regulating hemophilia gene - regulate TPPP? Potentially there will be developments to interpret genetic clues in diseases like ME/CFS**

I think there's less place to throw your [as in Doctors +++] hands up and say we can't understand, we can't treat, we can't --- help you.

I'm a bit concerned that I won't live to see this (I hit 60 recently) but some day this will be treatable --- some cases may already be --- look at the Nath study it seemed to find cases of other diseases (not common?).

*https://me-pedia.org/wiki/Tubulin_polymerization_promoting_protein
**https://www.s4me.info/threads/genet...lysis-2022-das-et-al.29445/page-3#post-452382

 

I don't expect to see much change in time to make a great deal of difference to me, to be honest. But I'm sure we'll find drugs eventually that offer worthwhile improvement, as in other chronic diseases, and we may learn how to lower the risk of developing it too.

Let's hope the genetic study gives researchers more information, as without some reliable clues, even strategies like AI-driven drug efficacy predictions haven't enough to go on.

 

I'd like to see my daughter in better health.

MRNA vaccines seem to have been produced in about 3 months --- OK there were a few decades of primary research ---
Also, presumably the parallel there is to a disease where a single gene is the issue and up/down regulating it, is a treatment --- unlikely to be that simple in ME/CFS.

I suspect it is long term --- but who knows --- we know so little
Discovering the underlying pathology/ies seems to be key --- until we know that we don't know if the tech/drugs --- is/is not there to solve it ---

Then there's the issue of mis-diagnosis with ME/CFS --- some people with ME/CFS likely have a disease which is known/can be treated.

 

That's mainly what drives me to contribute to research. I've long since reached an accommodation with ME on a personal level, but it breaks my heart to see young lives still being blighted from the teens onwards, as mine was—especially those who're severely ill.

 

There's a thread here re a recently published [long covid] endothelia dysfunction study* including a piece of equipment to measure same**

What to do think of endothelial dysfunction as a research area - e.g. testing whether this is a diagnostic test + this equipment**

@snowleopard any suggestions re research areas e.g. replicating the above study in ME/CFS?

*https://www.s4me.info/threads/sulod...ong-covid-2022-charfeddine.27942/#post-456467
**https://www.polymath.company/E4-Diagnose.html