Are we close to a "unified theory" of ME/CFS? If so, what is it?

[alex3619]

Therefore a unified theory would need to explain why enterovirus and EBV can trigger ME/CFS, but other viruses like norovirus cannot.

Yes. Two immediate possibilities are about location/tropism (gut, B cells, etc.) and pathological mechanism. There was a paper a few years back, and I forget the details now, that asked if ME were triggered by pathogens that infect both the gut and B cells. It seemed from what we know of triggering agents that this was the case. How this works is still unknown.

 

[lansbergen]

On the other hand with such large numbers of things that are dysregulated it might be that much or most of the variation we see simply arises from the extreme complexity of how all these things work together.

Yep

 

[Jonathan Edwards]

Thanks, @Hip.

I wonder what all those scientists at the IiME conference that Ron Davis thought were all on the same page were talking about.

I suppose my question is really whether the researchers feel that things are coming together or whether they feel they're all blindfolded and feeling just the nearest bit of the elephant.

To try to answer your question, @Sasha:

I think you may be reading too much into Ron Davis's statement to the extent that this was his first time at IiME, certainly in recent years and I think he may just have been reflecting on the common groundswell that has been developing amongst researchers across the world for some time now. In fact people presented on all sorts of diverse topics. The important thing is that everyone is listening to each other - so everyone may be working on their bit of the elephant but we are no blind to what others can see. If everyone starts working on the same thing in science that is not always a productive situation.

For me the metabolic findings do not really change the overall view that much. As Ponting points out, shifts in metabolites do not tell us anything about chains of causation - whether there is or is not a trigger from infection for instance, whether immune mechanisms are involved or whether it is an effect on the hypothalamus. We have to have an overall causal story to know what to do about it.

I would be very positive in that there is so much more information being generated now, and in all aspects of the problem. The information that will allow us to fit things together is not there yet but it may be not far out of sight. What I would emphasise is the continued need for independent groups to replicate each other's findings. We are still not seeing much int the way of direct replication studies being published. We need blinded samples being sent back and forth across the globe so that we can be sure about basic findings.

I would not be surprised in something significant comes out of Norway soon. The Norwegians looks if they may have realised that they may beat the rest of the world at this illness and they have a system that allows large amounts of funds to be channelled into very focused research.

 

[ash0787]

Hip its a leap of logic to go from accepting that the majority of cases are caused by viruses, to saying that all of them must be this specific type of virus which is somehow capable of persistently causing mitochondrial dysfunction, hence why I said " tend to start with wildly varying events ", also you didn't mention Lyme which I dont even know what it is but I hear people going on about constantly so it must also be a significant percentage of trigger events.

 

[Mark]

Having attended IiME for the last few years, each year I have got the impression of a field of research that is maturing and moving forward. This year I noted a few tentative but tantalising connections between different research findings. To me, the current situation seems like this: we have an increasing number of pieces of a jigsaw puzzle, and when you look at them all as you do at a conference like IiME, it is now looking more and more like they really are pieces from the same jigsaw puzzle. This is what's new, I think, because in the past there wasn't quite that same sense that all these pieces are actually from the same puzzle and might connect with each other. Now, one can look at some of the pieces and it looks like these two might well fit together, these two might go over there, and so on.

Looking at all the pieces, the fact that they look like they're from the same puzzle and will fit together at some point, all gives me more confidence that the research is along the right lines. But much more research will be needed before we can really fit the pieces together, especially because few of the pieces represent replicated research, so any of the pieces could be wrong. And of course we still might actually be looking at pieces from two or three different but similar puzzles. One thing I'm waiting for is for two apparently separate pieces of research to connect together. I think once we can put two pieces together, that might take us a long way towards being able to guess what the overall picture is, and where some of the other pieces might belong. That's the point at which we could start to talk about a unified theory, but so far, I don't think we can reliably fit any two pieces together.

 

[Biarritz13]

So to my mind, any unified theory of ME/CFS will need to explain why only these specific viruses, particularly coxsackievirus B and Epstein-Barr virus, seem to trigger ME/CFS. But such a theory would also have to explain how autoimmunity arises, and how the apparent energy metabolism dysfunction arises.

Are we saying that just because when we run a blood test the only thing that is reported/relevant/abnormal is the IgM for it?

For example, some (I don't know the numbers) patients with Lyme disease reports IgM for the EBV and for other viruses as well.

 

[aimossy]

It would be wonderful if the Norwegian Fluge and Mella team did make the first really significant big waves in the mainstream world. That would really be a sweet peice of news to read.

 

[BurnA]

It would be wonderful if Norway did make the first really significant big waves in the mainstream world. That would really be a sweet peice of news to read.

I am pretty sure they will.

The rituximab phase 3 trials will be by far the most telling research into ME to date.
If it turns out that those trials demonstrate a response in ME patients, well that is basically the starting point for a whole new field of research.

I think this thread is about 5 years too early.
When we know the rituximab results, when we know the OMF results, when we know the NIH intramural study results, when we know the Microbe Discovery project results, when the NIH collaborative centres are up and running, when we get more researchers into the field of ME, then it will likely take at least another 3-5 years for theories to be proven or not.

 

[RL_sparky]

I would not be surprised in something significant comes out of Norway soon. The Norwegians looks if they may have realised that they may beat the rest of the world at this illness and they have a system that allows large amounts of funds to be channelled into very focused research.

Wow, that would be awesome!

I think this thread is about 5 years too early.
When we know the rituximab results, when we know the OMF results, when we know the NIH intramural study results, when we know the Microbe Discovery project results, when the NIH collaborative centres are up and running, when we get more researchers into the field of ME, then it will likely take at least another 3-5 years for theories to be proven or not.

Well I got to dream for a few minutes! Your probably correct.
Another thing that I wonder about is Dr. Lipkin last December made a comment while visiting Dr. Peterson where he thought this disease could be solved in 3-5 years with the proper funding. I wonder what he is seeing to make that comment.

 

[aimossy]

I think personally in 3 years things will start getting to boiling point, but for a while I have had my money on 2018 being a big year partly due to what many here are saying.

 

[aimossy]

People often say that research is about 10 years ahead of where doctors are at and I tend to think that's true in many instances. But I also think when something majorly significant comes along for this illness, having that filter to actual doctors could end up being very fast if it is an amazing peice of research. I wonder if others think that.

Sorry if I'm derailing the thread. Maybe I am being overly optimistic.

 

[acer2000]

The Metabolomics data is interesting. However even if it is consistent across several studies, it doesn't say anything about what's causing the problem. I would think it's useful in helping narrow down the cause though.

The thing that worries me about the Rituxan studies is the same. Perhaps I've missed something but they seem to have figured out that this medication makes people feel better. But it is my understanding they still don't know why. I don't think that you can just assume that the illnesses autoimmune because it responds to a medication that is used in an off label sometimes for other autoimmune illnesses with varying degrees of success. By the same set of assumptions one could say that because Rituxan was originally approved to treat B cell lymphoma that CFS is really lymphoma?

My goal is not to discourage the progress, but I think that we need to get one level deeper here with both of these avenues of research to really understand what is driving the process.

 

[Hip]

Hip its a leap of logic to go from accepting that the majority of cases are caused by viruses, to saying that all of them must be this specific type of virus which is somehow capable of persistently causing mitochondrial dysfunction, hence why I said " tend to start with wildly varying events

The accumulated evidence we have for the likely infectious triggers of ME/CFS is not as solid as one would like, but I don't see any advantages of blurring what we do know into a vague "wildly varying events" and "anything goes" kind of idea about what may trigger ME/CFS.

And that applies to other chronic diseases too, many of which have been linked to infectious pathogens (see here for a list of pathogen-disease associations). So for example, there is a solid association between multiple sclerosis and Epstein-Barr virus, but no association between MS and rhinovirus.

I'd suggest starting a new thread on this subject if you want to discuss it more, as it is a bit off topic here.

Yes. Two immediate possibilities are about location/tropism (gut, B cells, etc.)

Indeed. It seems that EBV, HHV-6 and enterovirus (viruses that are closely associated with ME/CFS) can infect B-cells, which may set the stage for autoimmunity. See:

The 3 main viruses linked to ME — enterovirus, EBV & HHV-6 — all infect B-cells: autoimmune import?

 

[frederic83]

Epstein-Barr virus seems infrequent in Chia's list, at only 3% of ME/CFS cases, but I think the percentage of EBV-triggered ME/CFS is probably more like 20% of cases (I did a calculation here that indicates this). Perhaps he does not get many EBV patients, because he is more known for his interest in enterovirus.

Maybe you already know this paper, where they found between 15%-30% of EBV in the stomach of CFS patients (and control too). The exact number is not clear for me when I read the abstract. But it is close to your number. They also found 40% of PB19. These numbers could overlap as one patient could have one or more virus. I did not find the original paper to check.

 

[RYO]

I share the positive sentiment in regards to more data coming out recently. However, I believe we are only scratching the surface. I think funding for public and private research of ME/CFS is still woefully lacking. I think the Blue Ribbon Foundation's efforts to spur interest in young researchers is a step in the right direction.

 

[Barry53]

I would not be surprised in something significant comes out of Norway soon. The Norwegians looks if they may have realised that they may beat the rest of the world at this illness and they have a system that allows large amounts of funds to be channelled into very focused research.

Maybe a bit of healthy competition (no tasteless pun intended) is exactly what is needed right now.

 

[acer2000]

Do any of these studies differentiate between active new mononucleosis and re-activation? A lot of people say they got CFS after mono, but how do they know they didn't already have EBV and then the immune system lost control due to another event? If there was a way to figure this out it would be helpful. Although doing so is made difficult by the fact that CFS diagnosis isn't made until 6 months at least of not getting better from the original trigger. I did read a while back that someone was doing a study that was going to monitor people who got mono and follow immune parameters to see what happened if some of them got CFS. Not sure what happened to that one.

 

[BurnA]

I'd suggest starting a new thread on this subject if you want to discuss it more, as it is a bit off topic here.

 

[Ysabelle-S]

When are the phase 3 rituximab results due out? I have 2017 in my head for some reason, but I'm not sure if that's when the trial ends, rather than when the results come out.

 

[lansbergen]

but how do they know they didn't already have EBV and then the immune system lost control due to another event?

Good question.