It has been an unprecedented few weeks for ME/CFS. A much anticipated research paper in metabolomics came out in a top journal with striking findings, the community is now winning the war against the PACE trial – and the crowd went wild…
Metabolomics is a hot and relatively young area of research. Many patients wonder if the metabolism in our bodies is in someway impaired and a lot of patients who know about science and medical research, have been on the edge of their seats about this area of work and what it might find. This new paper, although not huge – did not disappoint.
The research paper titled ‘Metabolic features of Chronic fatigue syndrome’ was published in the prestigious Proceedings of the National Academy of Sciences. It hit headlines in many science outlets and was also covered by The Economist and the Washington Post.
The research is showing that patients are in a ‘hypometabolic state’ where key pathways are ‘dialed down’ and it is possible a metabolic signature could be used in future for diagnosis. Patients in the study met the Institute of Medicine, Canadian Consensus and Fukuda criteria. 612 metabolites were tested using Mass Spectrometry.
From the abstract, Naviaux and Gordon et all found:
Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites.
A hot spot for ME/CFS research
Yes, this is one paper, but it is exciting as there is promise of replication and previous research has shown anomalies in metabolism. Also, last year a paper published by Australian researchers titled ‘Metabolic proﬁling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients’, found correlations of blood metabolites and differences in energy metabolism pathways.
Not long after the PNAS paper released Dr. Maureen Hanson from Cornell University presented in a Solve ME/CFS Initiative webinar, details of her (yet to be published) research in metabolomics using Mass Spectrometry. She compared her findings with the PNAS paper. There were some similarities in the findings as well as extra pathways highlighted in her work. The key takeaway from this was that her work also showed a ‘hypometabolic state’ in ME/CFS patients.
Cort Johnson has done some excellent coverage detailing all this latest news. He discusses the PNAS paper along with the possible proposed theoretical cause here. He also covered the news from Dr. Hanson regarding the comparison of her work with the PNAS paper, and detailed some work in progress stating:
“The Naviaux study really caught our attention but a surprising number of other groups are doing metabolomics/metabolic/mitochondrial studies. McGregor in Australia, for instance, has been studying metabolism/metabolomics in ME/CFS for years. Here are some metabolomic / mitochondrial studies underway.
Hanson’s small ME/CFS metabolic study (under review now).
The Naviaux/Ron Davis OMF funded expansion of Naviaux’s recent study
Naviaux’s study comparing the metabolome of ME/CFS patients and other diseases
Hanson’s NK, T and B cell energy production study
The Lipkin/Hornig study tying metabolomics results in the blood to their gut findings.
The Bateman Horne Center/Watanabe Japanese metabolomics study. In what is clearly a Suzanne Vernon study, the Watanabe study, a Michael Hougton Canadian Cytokine Study, and Alan Light’s Autoantibody study will all use the same 100 patients samples – thus allowing them potentially to merge their findings…..
Nath’s metabolic chamber study in the Intramural study
Several studies from Armstrong and McGregor in Australia
The SolveME/CFS in house mitochondrial study (more on that later.)”
It is early days in metabolomics studies for ME/CFS. These research tools are very sensitive and large cohorts are needed. Many confounding factors have to be looked at and there will be differences across labs with methods and the type of technology used. A lot of work needs to be done to replicate findings across laboratories, as well as to fine tune, to pin down which metabolites are involved and home in on mechanisms.
This recent research news is exciting! Also, from the Microbe Discovery Project teams perspective, this makes Dr. Lipkin and Dr. Hornig’s Monster study at CII even more exciting. It will investigate metabolomics on 125 patients and 125 healthy controls, but is also analyzing across other key areas of research. This will help home in on mechanisms, find correlations and help generate more hypothesis. It is incredibly important to replicate findings.
Recently, Cort Johnson made contact with Vicky Whittemore and Marian Emr at the National Institutes of Health (NIH), in order to see what progress was happening with ME/CFS and funding. He wrote about what he found. One of the RFA’s (Request for Applications) mentioned is to “support ME/CFS collaborative research centers across the United States”.
It is not clear at this time if the funding in this RFA will include funding for the actual research these centers could carry out. Also, if there is going to be some funding – how much would be available. If the centers RFA does not include funding for actual research, it seems no RFA would be available in the foreseeable future specifically for this. The only option researchers have at this time is to hopefully gain an award of some funding through other standard NIH grant processes.
Without an RFA specifically for ME/CFS research, it will be much harder for CII to get their study funded by the NIH – all the more reason why we need your donations to make this work happen.
With the NIH dragging their feet in getting funding to strong researchers capable of big programmes of research it is heartening that collaborative efforts in advocacy to push harder than ever before are mounting. One, involving the #MEAction Network recently charged forward with a very successful campaign, managing to get 55 congressional representatives to sign a letter to the “NIH Director Francis Collins: 1) to consider in a timely manner the input received through the NIH Request for Information, and 2) to update Congress on the NIH’s plans for ME/CFS research through 2018.” You can sign up with #MEAction and get involved, they are always finding ways to help patients to participate in advocacy.
We are so grateful for the donations coming in to help CII’s huge research study and for all the advocacy going on to push for research funding!
The PACE trial
And, just as we are on the verge of breakthroughs with possible big clues as to why patients may have such difficulty with exertion, great news comes in regarding the fight for raw data from the 2011 UK PACE trial! The $8 Million dollar PACE trial was a publicly-funded clinical trial of exercise and cognitive behavioural therapy for Chronic Fatigue Syndrome. This research was very influential in encouraging various bodies to recommend CBT and graded exercise as the best available treatment for ME/CFS.
The fight to gain access to raw data was finally won after years of effort from many patients. More recently other academics and scientists have also joined the chorus with respect to misleading claims in this research. Only a day or so before this announcement of release of data, PACE authors published their own analysis with some of the original protocols. Their analysis was not published in a medical journal and did not include a key aspect of the changed ‘recovery criteria’. The #MEAction Network have written an article about this latest information.
To quote well known science blogger Simon McGrath regarding this graph:
New analysis from #PACETrial authors shows patients were right to claim changes to protocol made results look better
It is a very interesting time for ME/CFS, only yesterday the #MEAction Network launched a new UK and Global petition to stop Graded Exercise Therapy research trials for ME/CFS. Check it out!
Keep an eye on social media – we are sure there is more to come! Keep sharing!