Moving Toward Answers in ME/CFS

Woman in bed

Thinkstock/Katarzyna Bialasiewicz

Updated September 27, 2017: The National Institutes of Health (NIH) will award four grants to establish a coordinated scientific research effort on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The total cost of the projects for fiscal year 2017 will be over $7 million, with support from multiple NIH Institutes and Centers that are part of the Trans-NIH ME/CFS Working Group.

The grants will support the creation of a consortium made up of three Collaborative Research Centers (CRC) and a Data Management Coordinating Center (DMCC). The CRCs will each conduct independent research but will also collaborate on several projects, forming a network to help advance knowledge on ME/CFS. The data will be managed by the DMCC and will be shared among researchers within the CRCs and more broadly with the research community.


Imagine going to work or school every day, working out at the gym, spending time with family and friends—basically, living your life in a full and vigorous way. Then one day, you wake up, feeling sick. A bad cold maybe, or perhaps the flu. A few days pass, and you think it should be over—but it’s not, you still feel achy and exhausted. Now imagine that you never get better— plagued by unrelenting fatigue not relieved by sleep. Any exertion just makes you worse. You are forced to leave your job or school and are unable to participate in any of your favorite activities; some days you can’t even get out of bed. The worst part is that your doctors don’t know what is wrong and nothing seems to help.

Unfortunately, this is not fiction, but reality for at least a million Americans—who suffer from a condition that carries the unwieldy name of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a perplexing disease that biomedical research desperately needs to unravel [1]. Very little is currently known about what causes ME/CFS or its biological basis [2]. Among the many possibilities that need to be explored are problems in cellular metabolism and changes in the immune system.

A number of studies suggest that abnormalities in cellular metabolism, a complex biological process that the body uses to create energy [3][4][5], may underlie ME/CFS. A recent study of metabolite pathways in blood samples from people with ME/CFS reported a signature suggestive of a hypometabolic condition, similar to a phenomenon biologists have studied in other organisms and refer to by the term “dauer” (a hibernation-like state) [5]. A number of other studies have suggested that changes in the immune system may play a causal role in ME/CFS [6][7][8], either due to a post-infectious autoimmune process or due to a unknown chronic infection.

To date, most studies in ME/CFS have looked at relatively small numbers of people with ME/CFS and employed different methods—and rarely has a finding been replicated. Given the heterogeneity of the illness and complexity of the assays, rigorous confirmatory studies in larger groups of people with ME/CFS are necessary to provide the evidence base for effective therapy development. ME/CFS, as much as any other disorder, is in need of a concerted effort by the scientific community to understand its biological basis.

The NIH is committed to stimulating additional research to reveal the causes of this debilitating disease. ME/CFS is such a complex condition, affecting so many body systems, that we do not know where the answers will come from. Informed by results from a 2014 ME/CFS workshop [9], NIH initiated a call to action to all of its relevant Institutes and Centers in October 2015. The resultant NIH research effort, led by Trans-NIH ME/CFS Working Group, leverages an impressive scope of expertise across the NIH to attack this research gap.

The Trans-NIH ME/CFS Working Group recently solicited research applications to seed a nationally coordinated approach to understand the cause(s) and mechanisms of ME/CFS. In January, NIH issued two Funding Opportunity Announcements (FOAs). These FOAs seek to establish a research consortium for ME/CFS research, including a coordinating center to facilitate collaborative science among the sites and enable widespread data sharing. The consortium will provide a foundation upon which rigorous ME/CFS research can build to make new discoveries, validate research findings, and attract new investigators from various disciplines to study ME/CFS.

The research consortium is just a first step toward growing an innovative and vigorous research community to focus on this disease. The NIH is always open for other scientists to submit research grants on ME/CFS, and most NIH funding goes to these regular grant proposals, which are reviewed on a three times per year cycle. In addition, a variety of other research initiatives were recently launched. The NIH awarded seven Administrative Supplements to expand ME/CFS research in current grants. These projects use state-of-the-art technology to pinpoint genes that may be involved in the disease and to reveal how specific immune cells play a role in ME/CFS. Some of these projects will zero in on potential biomarkers, which are desperately needed to help with diagnosis and for tracking disease progression. Descriptions of these awards can be found at: https://www.nih.gov/mecfs/funding.

The NIH is also initiating ME/CFS research at the NIH Clinical Center in Bethesda, MD. Led by Dr. Avindra Nath, an expert in neurovirology and infections of the nervous system, dozens of investigators from seven of NIH’s Institutes and Centers will carry out an extremely detailed and comprehensive evaluation of several dozen people with ME/CFS, focusing on those whose symptoms can be clearly traced to an infectious-like illness and who have been sick for less than five years. These volunteers will undergo a comprehensive battery of tests, including blood draws and brain scans, to help researchers learn more about the clinical and biological features of this disease.

One of our goals is to improve communication about these research efforts to individuals with ME/CFS and advocates who have been affected by this devastating disease. We host regular telebriefings, which enable NIH staff to update the community on our activities and provide ME/CFS stakeholders with an opportunity to ask questions and offer their perspectives. You can learn about NIH’s ME/CFS-related efforts and briefings by visiting the ME/CFS website at www.nih.gov/mecfs. If you would like to receive periodic updates from NIH by email, please visit the ME/CFS website and click on “Join our listserv.”

We recognize and empathize with the suffering experienced by people with ME/CFS and their frustration that so little is known and so little research has been done to find answers. We aim to change that. The NIH is committed to unraveling the underlying biologic cause(s) of ME/CFS as swiftly as possible, and promoting research that will inform the development of effective strategies for treatment and prevention of this devastating condition.

Note: Walter Koroshetz, M.D. is Director of the National Institute of Neurological Disorders and Stroke (NINDS), NIH; Francis Collins, M.D., Ph.D., is the Director of the National Institutes of Health (NIH).

References:

[1] Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Institute of Medicine. Washington, DC: The National Academies Press. 2015.

[2] Workshop Resources, NIH Pathways to Prevention Workshop: Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Office of Disease Prevention, NIH. 2014 Dec 9-10.

[3] Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/ chronic fatigue syndrome. Fluge Ø, Mella O, Bruland O, Risa K, Dyrstad SE, Alme K, Rekeland IG, Sapkota D, Røsland GV, Fosså A, Ktoridou-Valen I, Lunde S, Sørland K, Lien K, Herder I, Thürmer H, Gotaas ME, Baranowska KA, Bohnen LM, Schäfer C, McCann A, Sommerfelt K, Helgeland L, Ueland PM, Dahl O, Tronstad KJ. JCI Insight. 2016 Dec 22;1(21):e89376.

[4] Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism. Germain A, Ruppert D, Levine SM, Hanson MR. Mol Biosystems. 2017 Jan 31;13(2):371-379.

[5] Metabolic features of chronic fatigue syndrome. Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, Baxter A, Nathan N, Anderson W, Gordon E. PNAS. 2016 Sep 13;113(37):E5472-80.

[6] Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome. Hornig M, Gottschalk G, Peterson DL, Knox KK, Schultz AF, Eddy ML, Che X, Lipkin WI. Mol Psychiatry. 2016 Feb;21(2):261-269.

[7] Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels. Nguyen T, Johnston S, Clarke L, Smith P, Staines D, Marshall-Gradisnik S. Clinical & Experimental Immunology. 2017 Feb;187(2):284-293.

[8] Illness progression in chronic fatigue syndrome: a shifting immune baseline. Russell L, Broderick G, Taylor R, Fernandes H, Harvey J, Barnes Z, Smylie A, Collado F, Balbin EG, Katz BZ, Klimas NG, Fletcher MA. BMC Immunol. 2016 Mar 10;17:3.

[9] National Institutes of Health Pathways to Prevention Workshop: Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Green CR, Cowan P, Elk R, O’Neil KM, Rasmussen AL. Ann Intern Med. 2015 Jun 16;162(12):860-865.

Links:

Chronic Fatigue Syndrome (Medline Plus, National Library of Medicine/NIH)

Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness (National Academies of Sciences, Engineering, and Medicine, Washington, D.C)

63 thoughts on “Moving Toward Answers in ME/CFS

  1. This is great news. MECFS patients have been waiting a long time for answers and with a bit of funding they might finally get them.

    There is a lot of promising work being done in the field of metabolism. preliminary evidence is hinting that something is inhibiting the normal metabolic processes from operating. With the right funding going to the right labs, solving the metabolism puzzle in CFS is certainly within reach and could, just possibly, uncover a cure!

  2. Please fund the big projects that Lipkin and Davis have planned. The planned increase in yearly funding for this disease (from $7 to $15 million) is not enough to make a difference fast enough. More appropriate funding would be around $250 million per year. There are probably not yet enough ME/CFS researchers to absorb this much, but Lipkin and Davis are clearly in a position to efficiently absorb substantially more funding. As they make progress, interest in this disease will grow.

  3. It´s certainly a good move but please speed up research. We need more money, we need more researchers into the field,…. We deserve it for 30 years of ignorance
    We need parity in funding.

  4. I suppose that your study limits test persons to have ME five years or less is due to studies which have shown differences in “fresh” patients and long-term patients. It is good news to read you take this difference in consideration. I also believe that it is important to understand this disease in the earliest state possible.
    However, as a long-term patient, of course I wonder if there will be research done for long-term patients as well? Especially when markers show up to be different in both groups, long-term patients could be left without help despite all research effort?
    An answer would be of great interest.

    • Yes, I agree. As disheartened as I am to see so many younger people (< age 40) being stricken with this disease, those of us who have suffered decades of disabling illness and medical abuse/neglect and/or have fought for all ME patients' rights until we no longer can, deserve some answers too before we die. I agree with the comment about $250K/year (just to start) – might be adequate to begin studying all stages of this illness.

  5. This blog nicely pulls it together about the front lines of research. Thank you. And I appreciated the statements of empathy – we rarely hear them. Also, I must agree with other comments about needing more funding, concentrating funding , increase subject base etc. My fears about what will and won’t be done before I leave the planet have increased since this new administration. Now in my 30th year of this “journey”, it is a trip I wish on no one and only pray that there are breakthroughs soon.

  6. Please provide the funding to research this neglected illness. I appreciate what you have said but to be of use, the money must follow. Please look at Ron Davis’ research needs. He gives of himself unstintingly. Thank you for making this statement which brings hope- help is needed urgently.

  7. Thank you for writing this blog, I appreciate everything that you can do to further the research for ME/CFS. We are in desperate need, please help us with our funding.

  8. Thank you for the honest acknowledgement of the devastation this disease brings and the intention to cure it. After so many years of neglect and abuse at the hands of the influential clique that control the UK response to ME it is a torch in this dungeon of superstition.

  9. Well it’s encouraging to hear all this, or it would be if the blog’s content weren’t then grotesquely contradicted by the Medicine Plus links underneath.

    I’m hugely grateful that the NIH is finally acknowledging reality, but talk is cheap & actions speak louder than words. Please fund Lipkin & Davis, reassess all links at Medicine Plus & bring that info in line with the IOM report, & indeed with your own words. And start putting your money where your mouth is.

    All that said it cant be easy going against the grain with this so well done for that

  10. It was a pleasure to read that the NIH has decided to finally put significant resources into understanding the biological basis of this most devastating disease. Long overdue, but very welcome as better now than not at all.

  11. Thank you, Dr Koroshetz and Dr Collins, for writing this article. People with ME/CFS need your strong advocacy to make meaningful progress towards elucidating pathophysiology and finding effective biomedical treatments. These kinds of articles are helpful in gradually changing the minds of those health professionals who believe that ME/CFS is just deconditioning and activity avoidance. Please do everything you can in terms of awareness-raising, funding and strategies to entice biomedical researchers into this fascinating field. Our lives depend on it.

  12. Considering the years of failure of the NIH to fund any reasonable research into this debilitating illness this article is, at most, slightly encouraging. Perhaps the NIH is now waking to actual scope of this illness in the general population. Maybe now those who are inflicted with ME/CFS and are laboring under the current shameful treatment regimes long supported by the government and offered by their Dr’s can now have a glimmer of hope that they are not to blame for suffering from a real illness. Perhaps this is a real sign that the NIH is finally waking up … still it is sad that our government has held off making any serious moves for so long.

  13. Thanks for this good blog. However, however, however, where is the increase in funding commensorate (sp) with the burden of the disease, which is just horrible. Help us!!! Thanks for writing. Can you do more?

  14. Thank you to Koroshetz & Collins for highlighting this important topic in a thoughtful way. Hopefully the larger medical community will take notice of this.The challenges are numerous, time is essential.

    History is grim but were still here and still optimistic. It says quite a lot of the stamina and strength of patients. The problem of course, is that good ideas and words won’t take us anywhere without substantial funding. Time is essential. It is much welcome that NIH itself will conduct rigorous studies. But much is already is in place for conducting larger studies- good collaboration among the real clinical experts of the disease, so let’s make way for good infrastructure, collaboration and well designed studies of proportion. Time is essential.

    Everybody acknowledge that science is what in the end will discover the cause(s) and make way for treatment possibilities, but in the meantime, as many already have pointed out – we can’t push science in front – meaning – passively avoiding doing other much needed work. – educate doctors, update information from novel clinics, face the “science” of PACE and so on. This may sound trivial for a die hard scientist and in some way it is, which make it so bad if health authorities do not work with such things. The major point here: such work can prevent much suffering and improve prognosis for patients in the long run. Should be of interest to health authorities, to economy and absolutely crucial for patients. Time is essential.

    Many will say that the name of the disease is the least important of things to work with, but the meaningless and horrific term CFS should be eradicated from the face of the earth once and for all. Words do matter and as we all know, this term captures close to nothing about the essentials of the disease, “fatigue” is merely some percentage of the problem. Secondly putting “fatigue” in a diagnosis will instantly make doctors turn their head away as fast as possible. They’re just not interested. It is horrendous to think of the click in UK, PACE and the impact it have had on patients all around the world. Patients are devastatingly harmed and killed.

    But thanks again for a well written blog that hits the spot and continue to give patients hope – which is all that has kept us alive in decades to date. Time is essential.

  15. I’ve been living with CFS for many years. Are there any future studies being conducted by the NIH in the near future.

    Thanks for your help.

  16. MS gets almost $100M per year in research funding. Why does ME, which has twice as many patients, get only $6-17M per year?

  17. My 25 year old son has been suffering with this disease for 2.5 years and is now bed ridden, in extreme pain, highly sensitive to most everything and unable to do most things that we take for granted. Prior to getting sick he was a vibrant person that completed college, started his own video business and travelled the world. After seeing over 20 doctors, some told us that it was in his head and with no diagnosis nor treatment was devastating and we felt hopeless. He was a person that was productive in society and enjoyed his life and now he has been reduced to someone that I no longer recognize and he is living a tormented life. Please continue to work towards finding a cure and don’t give up until we do. Much appreciated from a devastated mom.

  18. 5 years housebound and largely horizontal, now.
    Planned 2nd career gone, main hobbies gone.
    Social contact too tiring. Watching TV too tiring!
    One can’t even “fight” in the usual way: determination to do more makes things worse.
    (so much for the PACE trial)
    I would quite like my life back.

  19. Thank you! I have been sick since the early 90’s with this chronic and drastically life altering illness. It is not life threatening in the fact that it is not fatal which I believe is why it does not get the research money and efforts needed to find effect treatment and or a cure. That said, it still takes away the ability to function anywhere near normal. It leaves us unable to work and contribute to our communities as we desire to do. Most do not lose their physical life from this illness but we lose a great deal and so does the world. Thank you so much for your efforts!!!!

  20. Speaking of the PACE trial. How would the authors of this very flawed trial, rationalize those with gradual onset ME who had vigorous exercise programs for a number of years, before finally becoming too sick to continue their physical activity? I had a six year gradual onset following EBV, and exercised several hours/week, while at the same time gradually developing more and more ME symptoms. My diagnosis of ME was confirmed by Dr. Bruce Carruthers, the lead author the Canadian Consensus Criteria. Frequent exercise did not save me from ever deepening levels of ME, which I have now had for 32 years; mostly house or bed bound. Cognitive Behaviour Therapy has not helped either!!!!!!

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