The Mitochondria Man Gets His Money and The UK Goes MEGA: ME/CFS Research Moving Forward

Discussion in 'ME/CFS and FM News' started by Cort, May 19, 2016.

  1. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Good things keep happening in the chronic fatigue syndrome (ME/CFS) world and not all of them are on the federal level. Private efforts emphasizing collaboration and working together are continuing to produce surprising results and make waves. The Open Medicine Foundation (OMF) is a good example of that. In just the last month it's packed on another $1,000,000 in private donations and that means a new study is underway.

    The OMF's New Mitochondria Study

    The size of OMF's success may be surprising, but the fact that it is a success isn't really. Put together a visionary program with top research talent the money is hopefully going to flow, and it has; $5 million dollars of it since 2012 with the vast majority of it coming recently.

    This time $400,000 of it is flowing to the newest member of the team, mitochondrial expert Dr. Robert Naviaux. Dr. Naviaux's 100 person study will be looking in the smallest molecules in the body for the molecular roots of ME/CFS.

    The really, really nice thing about the study is what came before it. This is not an exploratory study; that study - an 80 patient study using patients from Dr. Gordon's and Dr. Cheney's practices - has been done. Using a process called metabolomics that study (unpublished) found evidence of a unique chemical signature in ME/CFS patient's blood; a signature Dr. Naviaux hopes could provide a diagnostic biomarker, and spur the development of new "rational therapies" to treat ME/CFS.


    Metabolomics is one of the newer 'omics" (genomics, proteomics) which advances in molecular characterization and data mining are thrusting to the fore in medical research. Metabolomics measures the metabolites or small molecules a cell produces as it does its work. Generally defined as any molecule less than 1 kDa in size, these metabolites provide a snapshot of what’s happening in a cell.

    Dr. Naviaux explains metabolism in terms of happens when our genetic heritage interacts with our environment. He uses the by-products or metabolites our cells produce to provide a new lens through which to “see” and understand the "inner world of the cell". He calls metabolomics “eavesdropping" on the collective conversations of the cells in the body".

    This is not just a mitochondrial or metabolomics study by the way. It's part of Ron Davis's grand plan to understand ME/CFS. Davis will extend the study by mating the genetic information he's gathering with the metabolomics data Naviaux is gathering.

    The first metabolomics database was created eleven years ago just down the road from Dr. Naviaux at Scripps University in San Diego. In January 2007, the first draft of the human metabolome was completed at the Human Metabolome Project (HMP) at the University of Alberta, Canada.

    Mass Spectrometers

    The big gun metabolomics brings to the research field is the mass spectrometer. It's proponents believe that mass spectrometer's (MS's) ability to discriminate between different molecules and different forms of proteins, will open up a golden age in biomarker discovery. MS's can detect small modifications of proteins or the presence of very small molecules that other techniques cannot.

    Current clinical assays are generally too crude to pick the small alterations of proteins and other cells that can play a role in disease. Many tests, for instance, to lump together different forms of protein that may produce different biological effects.

    The high cost of mass spectrometers, however, has limited their spread, thus far, as a diagnostic tool in the medical field. MS spectrometers need to demonstrate that they can provide clinically relevant information that other kinds of assays cannot in order for commercial labs to justify a substantial investment in machines and training. That's a work in progress.

    The search for metabolic biomarkers has been fruitful, though. The altered metabolism of cancer cells (in process called the "Warburg effect"), for instance, allows researchers to closely track the extent of cancer with PET scans. A mass spectrometer discovery of a small molecule metabolite called (R)-2-hydroxyglutate which appears to signal the transformation of healthy cells into cancers could ultimately lead to earlier diagnoses of cancer. MS's are being used in many medical fields including cancer, pathogens, diabetes and other chronic illnesses.

    Using the mass spectrometers in his lab Dr. Naviaux can measure over 500 small molecules representing over 60 biological pathways in a single sample of blood. In his first study of 80 patients he found evidence of small molecule/molecules in ME/CFS patients that he believes could a) provide a diagnostic biomarker and b) provide an opportunity for a new treatment approach.

    Naviaux's essay on the Open Medicine Foundation site suggests that the metabolite may be a signal produced by the mitochondria to communicate to the nucleus that the cell is in danger. This danger response, Dr. Naviaux believes, stops the cells from communicating with other cells in order to protect themselves. The result is a kind of system shutdown that would make sense in the context of chronic fatigue syndrome (ME/CFS).

    The other really nice thing about the Naviaux study is that it's already underway. This study looks like it will be completed as quickly as possible.

    The UK Goes MEGA

    The United States is not the only country that's thinking big. The U.K. is going MEGA: it’s aim - to produce the biggest ME/CFS study ever.

    Three approaches to solving chronic fatigue syndrome in the nonprofit/private realm seem to have prevailed. All have been successful.
    • Pilot Study Approach - The pilot study approach has been used with great success by The Solve ME/CFS Initiative (SCMI) and now the Simmaron Research Foundation. This approaches provides smaller amounts of money to gather the data needed to get large federal grants. This more open approach to ME/CFS has helped to paved the way for many studies including the repeat exercise studies, the Light's gene expression studies, Isabel Barao's immune gene study, Gordon Broderick's modeling studies, McGowan's epigenetic's study and others. (The SMCI has just announced it will fund a new grant package aimed at producing more pilot studies; more on that later.)
    • The Big Study Approach - The big study approach used by the Chronic Fatigue Initiative provides the money to do full-scale research projects. This approach resulted in the groundbreaking Lipkin/Hornig blood study, the Lipkin pathogen study and the Hansen mitochondrial study.
    • The Mega Study Approach - seeks to capitalize on progress in developing ever more effective data mining techniques to do large studies to get at the molecular roots of ME/CFS. This expensive, all in one approach requires bringing many investigators together to tackle ME/CFS. Thus far it's being employed by the Open Medicine Foundation and the MEGA alliance in the UK.
    Mega Studies Catching On

    The first attempt at a kind of mega-study approach probably was the Pharmacogenomics study put together by Suzanne Vernon at the CDC in the early 2000's. This early attempt brought together a diverse set of researchers to use advanced computational analyses to make sense of a wide array of clinical, genetic, laboratory and gene expression data.

    The next major mega-study type attempt was probably the Open Medicine Foundation's call for a sweeping approach to ME/CFS in 2012 which eventually coalesced into Ron Davis's End ME/CFS Project of which the Severely Ill Big Data project is a part. The Severely Ill contains a limited number of patients but involves one of the deepest dives into the molecular foundations of chronic fatigue syndrome yet seen. (The OMF just announced that the data collection phase of the study is done; it was wrapped up remarkably quickly).

    The NIH's intramural study involving everything from metabolic chambers to stem cells to ME/CFS mice to exercise studies to pathogen testing to autonomic nervous system, etc. constitutes probably the third mega-study ever undertaken in this disease.

    Now comes "The Grand Challenge"

    The Grand Challenge

    Now the UK is embarking on its own look at everything we possibly can, multi-dimensional, multi-researcher study aptly titled "the Grand Challenge". No more small, underpowered studies who results can be brushed off by the powers that be from this group. The goal of The Grand Challenge is to produce a massive, impeccably designed study whose results cannot be ignored. If it's successful, and there's no reason it shouldn't be if it gets the funding it need, it should indeed be a game-changer.

    It's projected to involve all the "omics" (genomics, proteomics, metabolomics) as well as immune, pathogen and other testing. An important goal of this massive project would be to ferret out the subsets we all believe are there.

    A recent workshop brought together leaders in various fields - many of whom have not been associated with ME/CFS before - to lay the foundations for the project. At the conclusion, the alliance behind the project, the ME/CFS Epidemiology and Genomics Alliance (MEGA), stated it will seek funding for it this year and hope to begin the project next year.

    Part of the project includes a genomics study of at least 10,000 adult and 2,000 child patients. In an MEAction piece ME/CFS patient and blogger Simon McGrath underscored what a unusual undertaking this is:

    “We’re talking about huge cohorts and there’s nothing like this anywhere in the world. Plus a lot of new researchers are coming to play. A whole load of talent from other areas is taking a keen interest in ME/CFS for the first time, ready to apply some smart technology — widely used in other, less-neglected illnesses — to our illness. Finally, it looks like we will see biomedical research in the UK on a big enough scale, and with enough new technology, to make deep inroads into understanding this illness — or illnesses.”

    A key member of the Alliance, Bristol University epidemiologist and genomics specialist George Davey Smith - whose resume extends to some 600 plus citations (and who loves to take on big projects like this) - stated that the study could yield a new era in ME/CFS research.

    With it’s focus on using the "omics" (genomics, proteomics, metabolomics) to understand ME/CFS, the Grand Challenge bears a resemblance to the Open Medicine Foundation/Ron Davis End ME/CFS Project. Hopefully the Grand Challenge and the End ME/CFS project will meet up at some point.

    The UK spent $8 million on the Pace study and got nothing but underwhelming results and a huge controversy on its hands. Now it has the opportunity to fund some real science. Let’s hope it steps up.
    Last edited: May 20, 2016
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  2. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Indeed. ME/CFS has many pieces I think. I hope somebody does a blog on Younger's presentation (for Health Rising that is :))
    Last edited: May 20, 2016
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  3. h3ro

    h3ro Active Member

    Dr Younger may very well find that Dr Naviaux is one step ahead of him in investigating the source of the brain inflammation. It seems that if Dr Naviaux's theory is correct (and it's certainly my favourite theory to date), the brain inflammation originates from his "Cell Danger Response".
    Last edited: May 19, 2016
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  4. h3ro

    h3ro Active Member

    Do we know if the study that was rejected by JAMA is likely to be published anywhere soon? I'm really impatient to see what's in it.
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  5. San Diego

    San Diego Well-Known Member

    I love that this major study is being done in the UK. I hope the PACEholes are taking notice!
  6. h3ro

    h3ro Active Member

    I haven't watched all of Dr Younger's youtube videos (not a fan of videos, much prefer articles), but the gist I got was that it's over-active, hyper-sensitized microglia. Has he gone any deeper into explaining it than that?
  7. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    We'll see! I think there are subsets all over the place. I just communicated with someone who did some really intrusive testing to see if her mitochondria were working - they were working fine - the thing that got her during exercise was her autonomic nervous system; it was pretty kaput!
  8. Lemnia

    Lemnia Member

    Does anyone know how to contact this UK study ? I'm in the UK and if they need additional patients to sign up in participation of the study I'm more than willing!
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  9. Tony L

    Tony L Active Member

    @Lemnia I think they are still in the process of securing the funding for this. If you are interested in donating blood to the UK ME/CFS biobank then that is now possible. They are currently recruiting around the London area, because they can only reimburse travel costs up to max £15, however they will take patients from other areas who can fund their own travel to London. I intend to travel up from west Wales next month.
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  10. Tony L

    Tony L Active Member

    Of particular interest to UK sufferers is this statement from the MEGA report

    Encouraging news.
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  11. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    The PACE trial is still the most expensive anything ever done in ME/CFS. Of the UK can fund that why give the other side a chance? How about $10 million for the Grand Challenge?
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  12. Arison

    Arison Member

    I think we can ignore the U.K research until the researchers involved in perpetuating the GET and CBT myth are fully out the picture. It's insulting to continue to involve White, Wessely, Chalder and Crawley in research not to mention the whispers the funding source being from Wellcome trust of Suzanne O'Sullivan 'it's all in your head' Wellcome book prize fame. It's just nonsense.
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  13. Rachel Riggs

    Rachel Riggs Well-Known Member

    @San Diego -- did you say PACEholes? :) :) :)
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  14. Arison

    Arison Member

    :) I'd never be that polite.
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  15. Rachel Riggs

    Rachel Riggs Well-Known Member

    @Arison It has a nice ring to it! :)
    San Diego likes this.
  16. Bertiedog

    Bertiedog Member

    I am not sure if I am similar to this. As long as I haven't got a throat or the beginnings of a UTI I regularly walk 8500 steps a week or more but if I push more than that I just run out of glucose to keep my blood sugar up. I know one's blood sugar is supposed to be fine when at a reasonably low level but I cannot do anything when mine is like that and my energy plummets, my heart races, I sweat profusely and walk like a drunk I am so dizzy.

    But after using my oxygen concentrator for 30-40 minutes a lot of energy comes back but not sufficient that I could go out and repeat the walk. I have to do more sitting down tasks and also some horizontal rest but definitely my central nervous system is massively involved in my illness.
  17. Tony L

    Tony L Active Member

    Oh come on, we need to be smart. Scientists are human with egos, often very large egos that need massaging with thanks and praise. I'm the first to condemn the so called science of White, Wessely and co. but if we can see hope of substantial funding for objective science by UK scientists then that is not something to ignore. Wessely and co. will only vacate the territory they hold when objective science forces the issue. Get behind those who now promote the search for objective truth in the UK. Top class science in top journals will defeat PACE and impact upon NICE.
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  18. San Diego

    San Diego Well-Known Member

    Why, yes. Yes I did. I was hoping someone would notice! hehe
  19. Simon

    Simon Member

    Hey, thanks for quoting me, Cort :)

    Let's hope this planned study does get funded.
    My guess is $10m is the minimum required for doing this study. One of the good things about this is that they are collecting samples that will be available to the research community for analysis - a 10k cohort (plus 2k children) of well-characterised patients would be a huge resource. Plus, omics researchers generally are big on open data so my guees is that their data will be available to others too.
  20. LavenderDojo

    LavenderDojo Member

    It's possible all these things are correct and interrelated. Mitochondria can release DAMPs (Damage-Associated-Molecular-Patterns); DAMPs can activate microglia (and if I recall correctly that's what Dr Younger is looking at, microglia); activated microglia can dysregulate the autonomic nervous system. Perhaps the signal cascade triggered by mitochondrial DAMPs can persist after the mitochondria themselves have recovered?