Which scientists and research groups would you want to bring to the ME/CFS research field

Suppose that you could lure research groups into studying ME/CFS, who would you like to bring to this field? Are there any top biomedical researchers who stand out or who have an expertise that might particularly suited in studying ME/CFS? Or: who are the most respected medical researchers that might be valuable to bring to the ME/CFS research field?

 

Great question!

David Sabatini needs a job—serious comment. He has worked on mTOR/rapamycin. Don’t want to litigate the baggage here https://en.m.wikipedia.org/wiki/David_M._Sabatini

Need buy-in from Arc Institute to focus on MECFS— these folks https://arcinstitute.org/team I tried to get OMF/RD to make some inquiries—don’t know how that went.

 

Any experienced metabolic researcher.

 

I don't believe that ME is a metabolic disease, so not those researchers. I do believe it's neuroimmunological (glial cells involved), but I don't know any specific researchers or groups to recommend.

 

I have no specific names but (as I've said often) ME/CFS is in need of detailed and extensive epidemiology, we are unlikely to see planned progress (as against the chance of a lucky strike) in the science of ME/CFS unless we have definitive data on multiple populations, giving much greater certainty on who gets ME/CFS, where the live, who they are, how the illness progresses, and what the actual population level burden of illness is and how any individual health system can actually meet that burden.

 

Michelle Monje is getting involved in “Long Covid”

https://med.stanford.edu/monje-lab/people.html

 

There are hundreds if not thousands of metabolic problems in ME. Its a side that lacks investigation, though we have way too many areas that lack investigation. It is probably (but not certainly) not a primary cause, but may be a secondary cause in that it induces complications and symptoms. If the immune problem is the itaconate shunt for example, or includes it, metabolism is involved though the cause is an innate immune response. Ditto for any other form of energy generation suppression.

In my view its a mistake to leave any clue untouched. Even if all we do is investigate the links between what we know of the metabolism and immune system its something. Also, neuroimmune issues are dealt with, typically, as neuroimmune issues. Yet we still do not know all the aspects of what that means. Ignoring clues is a mistake in my view, and metabolic issues, long observed, are a big set of clues.

Sepsis, for example, causes a massive shift in metabolism. So does an active innate immune system. Ron Davis' team is looking at this but we need other perspectives. According to Ron Davis our metabolomics is almost a match for that of sepsis. I do not think we understand sepsis either. We treat it as immunological, such as a cytokine storm, but its more than that.

Both the nervous system and immune system are impacted by metabolism, and our metabolism is so bizarre we are likely making too many assumptions about what this means. How do we know that the entire neuroimmune thing is not maintained by metabolic irregularities? We don't.

Finally I have been saying for maybe a decade, though on rare occasions, that metabolic rate testing might in many cases provide data similar to CPET and repeat CPET, though much less problematic. Does our metabolism go wonky during PEM for example?

If nothing else the data could help inform systems biology views of ME.

I do wonder if ME might not be a kind of chronic neuro-sepsis. The brain has its own immune function, and if that gets turned on by a pathogen that crosses the blood brain barrier, and gets stuck on, what does that do in the long term?

 

I think that's definitely a possibility, some kind of immune activation in the brain would make sense. It can influence the periphery enough to cause symptoms but without causing obvious damage - like IBS, brain gut crosstalk can cause severe symptoms but without major abnormality being found.

If that's the case though, we are fucked. As far as i know there are no drugs for this sort of thing. Minocycline and LDN are a joke. All neuro drugs either target the periphery, BBB or some target in the brain that has nothing to do with microglia. There is no drug that has been made with this purpose in mind. It will take 20 years for it to be made.


As for who i would want researching ME - i don't have any specific names but it would be nice to get a really accomplished person with an engineering background and a solid knowledge of biology. Like the people that engineer T cells for cancer. They could find new ways of analyzing cells and tissues. I think those are the kind of people who are more likely to get things done. Researchers with a pure medicine or biology background keep hovering over the same hypotheses for decades without ever making any progress. And it would be good to get proper animal models as well.

 

I think this is the best chance we have at fast tracking the disease.

Medical researchers spend their entire lives studying a single hypothesis they arbitrarily picked and when all is said and done you still don't even know if it's true, let alone how to cure it.
When you have thousands of researchers all doing different things it can work but we will never have that much attention and research on ME. It would be far better in my opinion to get someone from outside the field who knows how to do hard science that is result oriented rather than hypothesis driven.

 

Very good and apt question. I've been looking at Stafford Lightman (Bristol) in response to this and will probe further on the conundrum (I know he has been looking into cortisol and HPA for a long time and I know the potential for concerns, but on the other hand someone who can understand the 'systemic' stuff and do new methods to tackle these issues potentially sounds the ticket). I thought it might be to look into the research group but not there yet.

Anyway I'm linking to the following, because it is a magazine type article (getting to know) where he talks about one ambition being to measure people at home over 24hr periods being a bit next focus: https://endocrinologyblog.org/2018/...on-of-the-hypothalamo-pituitary-adrenal-axis/

I thought it was interesting.

And then I think of @PhysiosforME and their work, and how this might combine with Workwell 2-day CPET type research (hoping that moves on into looking at the full spectra of severitiy, but also the 'full run/gamut' of PEM from before exertion to many weeks after, so moves along those types of lines)

Another article on him mentioned his move into using systems biology - and I think this (and perhaps other interdisciplinary areas that started to have funding about a decade + ago, with new centres springing up using things like maths and computer science approaches for biology, chemistry etc) is an interesting one to look into.

My only worry isn't necessarily all the guff about rumours like 'CFS patients difficult or undeserving' or whatever etc (although that is there) putting people off, but the recruitment side and getting better diagnoses and registers of people who have PEM ME/CFS. And eventually potentially types.

I think we need to think about how we can provide an 'attractive problem' (in a mathematical/science sense) - and I'm aware things have been so bad from so many angles then all these bits are an issue and it is where do we start, but wonder whether 'on all of them, but nudging the right bits to make the next part of the other areas more possible' ie thinking of it like a project management approach of what stands in the way of certain areas getting involved (because they'd never get funded for all this sorting and recruiting which is off their remit).

Maybe combining in @PhysiosforME with the above sort of thing might be ways to help this on an initial project basis

OK I know I'm going a bit off-piste here

 

Anyone in particular?
David S. Wishart (https://en.wikipedia.org/wiki/David_S._Wishart) fits this profile and he seems to be getting into this space, at least indirectly.
His team collected my blood a couple of months ago for a Long Covid study, which was sent to Canada's national metabolomics laboratory. But his interest is commercial. He co-founded a company called MolecularYou, which is planning to offer a metabolomics test, and I do not think we have a lot of options on the market right now that offer that. Hope they find something meaningful.

 

We needs teams - interdisciplinary and picked for skillset not necessarily medical research disciplines - we need to look at this from the outside , and be capable of looking at the whole and the parts and how they work together- this is difficult to do when medical research appears so siloed . I don't know names , but have often thought :-

Non medical systems specialists- potentially someone who has worked in climate science . This is a complex systems condition and needs those who are conversant with complex models with non linear processes and effects.
The smallest input may have the biggest effect .

Engineers for similar reasons - perhaps those who have worked with complex control systems?

Physicists / biophysicists ( is this a thing?) cancer research seemed to get a new sense of focus once they got involved .

Maths/IT - network analysis and " fancy pants" maths specialists .

Genetics - though I think epigenetics may play a far bigger part than genes per se.

 

Agreed. Big picture people. People who can organize data. We need more cohesiveness.
And, replication of promising studies.

 

I think this is badly needed.

 

This is the wrong way to go. Animal models do not work.

 

There may be a range of natural supplements or treatments that might work. All requiring clinical trials of course. Also there are a great many drugs that never made it to market, which can be rapidly tested on testbeds (if we build them) and then go to clinical trial. Then there are potential drugs from repurposing. Five years is feasible in these cases, with most of the time being on a large clinical trial.

An entirely new drug might be developed in ten years if there was enough interest. Twenty years is if its slow and steady research. I have been waiting nearly 55 years for a cure. To me even twenty years sounds better than never.

 

These days cell line studies from actual patients are a great early alternative. They can also be genetically modified if necessary, to alter specific genes if we can identify them (such as gene knockouts etc.). For an even earlier alternative in testing we have genetically modified yeast, which OMF has been working on I think. Of course you need to know what gene to modify to do this.

Sometimes animal models do work on rare occasions, but are super unreliable. Even if drugs work on the animal they might not work on humans. You also have the problem that an animal model means you have to have at least a basic understanding of the pathophysiology. We are still trying to get there.

 

There are many studies looking at a large array of things that have had findings, like the metabolomic studies. I think we need studies that combine all the promising broad tests on a single cohort. Comparing between cohorts is very problematic. Something like this would definitely require a competent team.

 

While that is true, it's also unfortunately true that there are limited resources available for ME research, and there is simply not enough available to study every single clue to the extent it should be. If we spread the available resources equally to all the possible clues/pathways/hypotheses, no one would get enough to do anything worthwhile. Since ME's root cause has continued to evade discovery, it probably requires expensive equipment and experts (such as studying the brain cells in detail in vivio). When the question becomes "How should the limited resources be allocated to provide the best return on investment?", I think that downstream effects of the disease should get lower priority.

I do like the idea of getting some engineers involved. Applied science rather than just theoretical science. There's a different mindset and set of goals. Theoretical scientists may be too focused on publication, while the engineers might see it as "Here's a problem, let's fix it." I have an engineering background and see my ME as a black box problem: I can't see inside the skull, but I can observe what happens when I change input factors (food, activity, etc), so I can come up with models that match those responses. The engineering approach might involve "whacking it with a hammer" (meaning potent chemicals, electrical zaps, etc), but if that works, I'm fine with that.