What’s the Current State of ME/CFS Research?

In recent years, myalgic encephalomyelitis (ME) has reached a medical milestone: it’s just about believed.

For decades, the disabling illness (also known as chronic fatigue syndrome/CFS) was maligned within medical education and disbelieved by most doctors. A few dogged researchers tried to substantiate the malady, but their work never dented the pedagogical skepticism.

Little progress was made. Patients remained untreated and doubted.

Then the COVID-19 pandemic descended across the world. Millions died and millions more were left with crippling, unshakable symptoms. Most reported feeling disabled from chronic fatigue. Soon enough, this condition was dubbed long COVID.

To understand this “new” illness, research studies popped up in multiple countries. Their findings demonstrated that, in many cases, long COVID was largely indistinguishable from ME.

While long COVID patients are still calling for more substantial, interventional studies to find treatments for their illness, there’s no doubt that the last few years of research has been far more significant than the preceding decades of ME literature. Crucially, the condition is (mostly) accepted by medical professionals.

This recognition has spilled over into ME, finally validating the experiences of countless patients who, for years, have had to manage their illness and the disbelief that surrounded it.

So, does this mean thorough, interventional ME studies are now on the horizon? Possibly. In 2022, the US National Institute of Health (NIH) announced the development of a ME/CFS Research Roadmap Working Group to identify “research priorities to move the field toward translational studies and clinical trials”.

Two years later, the group is seeking feedback on its chosen research priorities, which include the nervous system, immune system, metabolism and genomics.

And the NIH group isn’t the only one investigating these areas of interest.

ME Research UK is a UK-based charity that commissions and funds scientific research into the causes, consequences and treatment of ME.

Technology Networks caught up with the charity’s resident Science Writer, Dr. Emma Slack, to find out what research it’s currently funding and what promising findings have recently been made.

Leo Bear-McGuinness (LBM): What kind of research does ME Research UK fund?

Emma Slack (ES): ME Research UK funds high-quality scientific biomedical studies investigating the causes, consequences and treatment of ME/CFS. The charity funds research at all levels from PhD – such as that currently being carried out in Australia by Tina Katsaros and her supervisor Dr. Sarah Annesley, which is considering the cause–effect relationships in the mitochondrial energy inefficiency in ME/CFS – through to research projects. For example, Dr. Rob Wüst and colleagues in the Netherlands are looking at muscle microclots and microvascular pathology in ME/CFS, and Prof. Simon Carding and colleagues in the UK are exploring whether gut viruses have a role in the development of ME/CFS.

While much of the research funded at the moment is lab-based, ME Research UK has also funded projects that consider the experience of living with the ME/CFS, such as that by Victoria Strassheim and Prof. Julia Newton, which documented the lived experience of severe ME/CFS.

A major failing in the ME/CFS research field is the lack of active researchers. We have a step-by-step approach; we fund PhD-level research, aim to award a fellowship and provide full grant funding in the hope that, as happened with Prof. Julia Newton’s Newcastle University team, they are able to apply successfully for National Institute of Health and Research (NIHR)/Medical Research Council (MRC) funding.

LBM: What kind of studies would ME Research UK like to fund in the future?

ES: The charity would like to continue to fund high-quality scientific – biomedical, studies investigating the causes, consequences and treatment of ME/CFS. ME Research UK funds projects in all areas related to the biology or treatment of ME/CFS, but the charity’s main areas of interest include:

• Muscle fatigue – underlying mechanisms and potential therapies
• Brain and nervous system – structural and functional changes
• Immune system – autoimmunity and the role of specific antibodies
• Metabolomics and the search for diagnostic biomarkers
• The symptomatic impact of ME/CFS on other organ systems.

In addition, the charity encourages applications for research projects that use diagnostic criteria for ME/CFS which require post-exertional malaise (PEM) – said to be the cardinal symptom of the disease – to be present for a diagnosis to be made. Historically, studies have used varying diagnostic criteria for ME/CFS which all require different symptoms – not always PEM, to be present for a diagnosis of the disease. This makes comparing results between studies extremely difficult, and delays research progress.

It is also important that future projects take into account both the heterogeneous nature of ME/CFS – such as disease severity, length of disease, the delay to diagnosis and co-morbidities, in addition to the diversity of the population with the disease such as age, sex and ethnicity.

However, we are acutely aware of the charity’s funding limitations. Research is expensive and becoming more so. Ideally, we would wish to fund studies with larger cohorts of participants – the results of which could have a greater impact – build an ongoing funding relationship with successful research groups (which has been achieved with Prof. Leighton Barnden’s studies in Australia investigating the brain and ME/CFS) and build a sustainable ecosystem of researchers from PhD-level to principal investigators.

LBM: What do you make of the current state of ME research? Has the field changed much in recent years?

ES: There have been significant advances in ME/CFS research over recent years. However, much more high-quality research is still urgently required. Results of research are all too slowly changing attitudes within the scientific community and healthcare professionals, and too slowly are central funders acknowledging the chronic under-investment in ME/CFS research, which has existed over decades.

Internationally, having attended ME/CFS research conferences over the past couple of years, including the recent “16th Invest in ME Research International ME Conference 2024”, and “Unite To Fight 2024”, it is clear that there have been significant advances in actual research into the disease, these include:

1. The involvement of people with lived experience in research. Although this is not a change exclusive to ME/CFS research, there has been a notable shift towards methods that encompass patient and public involvement and co-production.
2. Although not new knowledge, it is also worth re-iterating that studies now clearly show evidence that ME/CFS is a biological disease – such as (but not limited to) abnormalities in:
   - The immune system, such as increased levels of autoantibodies specifically against proteins involved in cell communication for essential body functions like blood pressure regulation
   - The circulatory system, such as reduced blood flow to the brain, reduced supply of oxygen to tissues of the body, endothelial dysfunction and oxygen consumption attainable during physical exercise
   -Energy metabolism, including an abnormally low metabolic rate and an increase in lactate, the product of anaerobic metabolism
   - The importance of drug re-purposing and clinical trials. For example, “The Life Improvement Trial (LIFT)” study, which will investigate two drugs pyridostigmine (commonly known as Mestinon) and low-dose naltrexone (LDN) separately and together as a combination.
3. Recognition of the heterogeneity of ME/CFS and how this complicates research. ME/CFS presents differently amongst different people, and even within the same individual over time. This complicates research, limits comparability between studies and delays research progress, contributing to the stigma related to the disease.
4. Recognition of who is missing from research and a push for researchers to develop methods that will include these under-represented populations. Traditional research methods are often not accessible to those with very severe and severe ME/CFS, who make up approximately 25% of all people with ME/CFS, which means they're often under-represented in research. There are also other minority groups, such as ethnic minority groups, who are underrepresented in research.
5. Additionally, new technologies (such as DNA sequencing for DecodeME) or the development of 7-Tesla brain imaging (used in Prof. Barnden’s work) are making an impact, and collaborative working between researchers studying different bodily systems has certainly increased.

The results of research, coupled with the prevalence of the disease and its symptom burden, has resulted in moves to remold the research agenda. In the US, the NIH ME/CFS Roadmap offers a route to transformative change in ME/CFS research. In both Germany and the Netherlands (28.5 million euros 10-year program) they have strategic ME/CFS research collaboratives newly established, whereas the anemic Delivery Plan for ME/CFS [in the UK] is already two years late and is not anticipated to be delivered until winter 2024/25.

In the UK, the mantra remains that MRC is willing to fund ME/CFS research, but it does not receive suitable applications. There cannot be a strategic research initiative without a research base, but there is not a research base because central funders reject applications and appear unwilling to invest in ME/CFS biomedical research at an early stage. It is a perfect Catch-22 and helps explain why ME Research UK has stepped in with our Step-by-Step approach.

The challenges facing the field are well-known and have been for decades. In 2006, the Gibson Inquiry delivered its report and said: 

“This group believes that the MRC should be more open-minded in their evaluation of proposals for biomedical research into CFS/ME and that, in order to overcome the perception of bias in their decisions, they should assign at least an equivalent amount of funding (£11 million) to biomedical research as they have done to psychosocial research. It can no longer be left in a state of flux and these patients or potential patients should expect a resolution of the problems with only an intense research program can help resolve. It is an illness whose time has certainly come.”

LBM: Could you describe the organization? How does ME Research UK source funding? How does it choose which studies to fund?

ES: The principal aim of ME Research UK is to commission and fund high-quality scientific biomedical investigation into the causes, consequences and treatment of ME/CFS. The charity invites grant applications (when there is an open call) from researchers wishing to conduct studies falling within this aim.  

Funding is available to support scientifically robust biomedical studies at appropriate host institutions worldwide, and all projects are financed through the generous donations of the charity’s supporters – without whom, the research would not be possible. These supporters are mostly those affected by the disease and their family and friends either through direct donations, active fundraising or legacies. We receive no central funding; most companies wish to see local and tangible returns for a donation and so medical research is unattractive to them, and lottery funding is not available for medical research. ME Research UK has invested over £4m in research since its inception in 2000 – that is 5 PhD-level projects and 68 research projects.  

All funding applications submitted to the charity undergo the rigorous five-step review process outlined below:

• Step 1: Applicants submit an outline research proposal
• Step 2: Outline proposals received by the closing deadline are reviewed by ME Research UK’s Science Committee
• Step 3: Successful applicants are invited to submit a full grant application
• Step 4: Full grant applications received by the closing deadline are reviewed in detail by external peer reviewers and ME Research UK’s Science Committee
• Step 5: Science Committee makes recommendations with final funding decisions being made by the Board of Charity Trustees

Within this process, the science, research methodology and cost of proposed projects are considered in detail, alongside the research outcome’s potential benefit to people with ME/CFS.

To guarantee that the review process not only assesses the science, but also what is important to people with ME/CFS, all submitted applications are reviewed by ME Research UK’s Science Committee – members (some of whom are external to the charity) include experienced scientists, experts in ME/CFS research and those with lived experience of the disease.

ME Research UK also submits all full applications to peer-review. This is where researchers with expertise – such as knowledge of a complex methodology or experience in a certain area of ME/CFS research – are invited to review grant applications. Peer reviewers are external to both the charity and the Science Committee and provide impartial feedback on the quality of submitted proposals using a standardized assessment system. Within this feedback, peer reviewers are asked to make a recommendation to the Science Committee as to whether an application should be funded or not.

Full details of the application and review process can be found on ME Research UK’s website.

Dr. Emma Slack, Science Writer at ME Research, was speaking to Leo Bear-McGuinness, Science Writer and Editor at Technology Networks.

About the interviewee:

Dr. Slack is a science writer and researcher. She is a researcher associate at Newcastle University’s Population Health Sciences Institute Faculty, where she has worked on a number of projects studying parental and child health, pregnancy, long term and fatigue related conditions and health inequalities.