A brightening future: the state of ME/CFS research

A brightening future: the state of ME/CFS research

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Although there are no treatments for ME/CFS on the horizon, things are looking up thanks to recent findings and a substantial increase in the amount of high-quality research. The field still needs much more funding.

Do you remember the buzz around rituximab? Oncologists Dr Fluge and Professor Mella had noticed something interesting when they treated their cancer patients who also had ME/CFS with the cancer drug rituximab: the patients’ ME/CFS symptoms improved dramatically. In 2011, Fluge and Mella’s small trial of rituximab as a treatment for ME/CFS produced promising results. A larger clinical trial followed but, last November, the researchers revealed that the treatment was not effective for ME/CFS.

As a result, things feel a bit flat right now for patients. People with ME remain desperate for treatments but there is no clear path to effective therapies. Yet I’m optimistic that things will improve. The ME/CFS research field is the strongest it’s been and there are good reasons to expect progress in understanding the illness – understanding that should drive the development of treatments.

Reasons to be cheerful, Part 1: promising findings

Most of the first 20 years of my illness have seemed like a long night of ignorance when it comes to understanding ME/CFS. Despite the efforts of small and dedicated but underfunded research groups, I saw little progress.

But things have really picked up in recent years, with several promising findings. A major focus for researchers has been on the ability of ME/CFS patients to produce energy. The two-day maximal exercise tests by Workwell and others show an unusual drop-off in the performance of ME/CFS patients on the second day. Findings from other research groups studying energy production at the molecular level, using metabolomics and the Seahorse technology, indicate problems with energy metabolism.

An analysis using a large biobank found that women with ME/CFS were slightly more likely to have one gene variant of the mitochondrial ornithine transporter protein. Such a genetic association, if confirmed, would demonstrate a causal role for the protein in the disease, in some. The ornithine transporter plays a key role in the urea cycle, which removes ammonia from the body.

There have been many findings of modest immune dysfunction over many years, notably a reduced ability of the killing effectiveness of natural killer cells. But in 2017, Dr Mark Davis at Stanford reported substantial levels of T-cell clonal expansion in patients, similar to that seen in multiple sclerosis and infections. If these dramatic findings are confirmed, this sign of immune activation could be a breakthrough in understanding the illness. It could even lead to identifying what is activating the immune system, and then to treatments.

One active theory is that the core problem of ME/CFS is in the brain, which drives the rest of the problems in the body. The most striking finding in support of this is the 2014 finding of activation of the brain’s main immune cells, the microglia.

And, of course, Dr Ron Davis’s research has generated a lot of attention, particularly his work aiming to find cheap diagnostic tests. One of these, the nanoneedle chip, reveals remarkable differences between blood samples from ME/CFS patients and those from healthy controls – but only when an energy demand was placed upon the white blood cells. In a linked “plasma swap” experiment, plasma from ME/CFS samples made healthy cells behave like sick ones, while plasma from healthy samples made ME/CFS cells behave like healthy ones.

Reasons to be cheerful, Part 2: the research field is getting stronger

These are all promising findings that might in time lead to treatments. But the ME/CFS research field itself is getting stronger, substantially increasing the chances of further important discoveries.

There are good things happening across the board in research. New blood is coming into the field: for example, Dr Derya Unutmaz, an immunologist specialising in the role of T cells in chronic disease, joined the fray within the last five years and now heads one of the new NIH collaboratives. New and existing researchers are also applying new technologies such as omics (including metabolomics). These new technologies are helping researchers to identify disease abnormalities that simply couldn’t be seen before.

Researchers are also scaling up their studies, recruiting larger cohorts, and diagnosing those cohorts more rigorously. The UK ME/CFS Biobank is making such large, well-defined patient cohorts available to many more researchers. Bigger studies using carefully diagnosed patients are more likely to produce findings that hold up over time.

In the past, isolated research groups often applied a single approach to a problem, such as using cytokines to look at the immune system. Dr Alain Moreau compared this approach to blindfolded men feeling different parts of an elephant and all reaching different conclusions about what it was.

elephant parable

Increasingly, researchers are collaborating to apply several techniques at once, giving a better chance of seeing the whole elephant. For example, Dr Maureen Hanson’s NIH-funded collaborative brings together experts who between them will look at gene expression, neuroinflammation, extra-cellular vesicles and the impact of a two-day exercise test.

Researchers are also coming together in other ways. This year has seen four conferences: the Canadian collaborative conference in Montréal, Invest in ME Reseaech’s in London, the CMRC’s in Bristol and the Open Medicine Foundation’s Working Group Meeting at Stanford. The three NIH collaboratives will be working together on a single, shared project. Europe has its growing EUROMENE network to foster collaborations.

And, at last, replication attempts of findings are becoming more common. For example, Dr Bob Naviaux and colleagues have a replication in hand of their original, striking metabolomics finding. Several other groups are pursuing or have published similar work using metabolomics. Mark Davis is looking to replicate his approach on T-cell clonal expansion in a larger cohort, and in the UK, Professor Chris Ponting is planning an independent replication of the work. Meanwhile, Dr Shungu, in Dr Hanson’s collaborative, will replicate the brain immune activation study – as will Dr Michael VanElzakker at Harvard Medical school.

Such replication attempts are critical in establishing what is real and worth pursuing, and what is not.

Even the funding situation has improved somewhat. The NIH has roughly doubled its spending on ME/CFS and is planning to invest around $35 million in its three new collaboratives. That’s still nowhere near enough money, given the disease burden and the lack of progress to date, but it is an important start.

Meanwhile, the Open Medicine Foundation has already raised over $14 million for ME/CFS research and is investing in programmes at both Stanford and Harvard universities.

In the UK, things are moving much more slowly. Research remains on a small scale, but even here there is hope. The CMRC is striving to persuade the Medical Research Council (MRC) to commit substantial funds to ME/CFS research.

Future prospects

Overall, and internationally, ME/CFS research is gathering momentum. The buzz of rituximab has been replaced by the growing hum of work on several lines of promising research. There’s no knowing when there’ll be a breakthrough leading to treatment, but I’m optimistic that there’ll be substantial progress over the next five years.

At worst, there should be a better grasp of key areas, including immunology, energy metabolism and the microbiome. As Professor Jonathan Edwards told me in an email, there are now “[E]nough people working on the problem of ME/CFS for the big negatives to firm up and the real leads to emerge.”

At best, as Dr Ian Lipkin predicts, researchers could identify the cause of the illness in some subtypes, with one or more of these subtypes being readily treatable.

There is, I believe, a brightening future for patients. How bright, and how soon it will arrive, remain to be seen – much will depend on the big funders, including the NIH and the MRC, investing properly in ME/CFS.

Comments are open. Please do join the discussion here or at the Science for ME forum.

Image credits: Sky, (c) Can Stock Photo / floyduk;  Elephant cartoon, Slideshare.net.

16 thoughts on “A brightening future: the state of ME/CFS research

  1. Just to stress that while things are looking up, there would be more research, moving faster – a brighter future, arriving earlier – with appropriate levels of funding of ME/CFS research. This remains a small field operating on a shoestring compared with other illnesses that have a similar disease burden.

  2. Hi Simon,

    Thank you for the newsletter/blog, and for all your clarifying articles.

    The title of this newsletter struck me. I have been ill since 1992 or there abouts, and I feel the same, that the future is brightening for us. I have turned 60 this year, and I would be perfectly satisfied to just know what it is that is causing this terrible disease before I die. Treatment would be welcome too, but the amount of research now and the things they find that are wrong with us, it makes me happy. Finally, finally, he?

    Warm regards, Bettine


  3. Well done Simon. Excellent blog once again my friend. Now get some rest – you deserve it! 🙂

    Speak soon.


  4. Thanks – your article reached me on a very bad day of a huge flare & provided a needed reminder that there is indeed reason for hope. I surprised not to see Dr Younger of UAB mentioned – he is doing definitely part of the reason for hope.

    1. Glad it helped. Do you know if there was ever a follow-up to is daily leptin study? I saw Cort‘s blog about his latest brain scanning work, but the details weren’t clear and I think it’s a bit early to mention it. Hopefully, more details will emerge in the Stanford symposium.

  5. Thanks Simon, any positive slant always helps me…even though we don’t know when answers will come. Really hope funding picks up. Thanks for all your work.

  6. I think the elephant being evaluated in pieces is an apt analogy. It does still feel like it might not just be an elephant, but a few different animals with similar characteristics. I hope that as research progresses, we see a clearer picture unfold, and perhaps by properly sorting out subgroups, the characteristics of the disease can be better mapped.

  7. I am an Alternative Practitioner and have treated and taken an interest in ME/CFS for the last 20 years. It seems there has been little real progress in finding a viable treatment. However I have a completely different hypothesis to explore but cannot find anyone to listen. Might you be able to help?

  8. Thankyou so much for this well written summary of current research and the glimmer of hope that one day there could be an explanation for this debilitating thing. I have had a tough few days and it is so reassuringto read something like this. Thanks again.

  9. CFS 22yrs of Pain in arms and legs very weak, Firtly 6 months in bed hubby showered me and fed me ,fell over a few days ago because of weak painfull legs This relapse lasted 8 yrs now. Memory I know my memory is not too bad by Brain mri Just Done 2weeks ago,But memory is just terrible . Every Morning I have to sit around with taking 1×600 mgs Gabapentin not too bad with the pain then ,but always exhausted most of Day 70 yrs of age, hope a cure is close would love to have a normal LIFE.

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