Hanson's Metabolomics ME/CFS Study Validates Naviaux's Core Finding

Discussion in 'Chronic Fatigue Syndrome (ME/CFS) Research' started by Cort, Sep 4, 2016.

  1. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    A Great Addition to the ME/CFS Field

    hanson, maureen 2012.jpg
    Dr. Maureen Hanson has been all over the place in chronic fatigue syndrome (ME/CFS) lately.
    Hailing from Duke and Harvard and now at Cornell she has quite a pedigree. With a family member with chronic fatigue syndrome (ME/CFS), she also has a personal stake in this disease, and has penned several editorials supporting ME/CFS research. Her "Be Aware and Beware" Huffington Post blog and her Congressional Hill post "When Hoofbeats are Zebras" showed that she's not afraid to leave the laboratory and get out and advocate. At every opportunity she makes it very clear that ME/CFS is a real disorder. Her last gut study went viral and was picked up by over 50 media outlets.

    She recently spoke at the Invest in ME Conference, and at the Simmaron Patient event, and is on the scientific board of the Simmaron Research Foundation.

    As and added bonus she appears to be very good at getting NIH grants. She first popped up in ME/CFS with a grant to study XMRV in 2011. Since 2011 she's gotten three R21 grants on ME/CFS, and is a collaborator on a big RO1 immune functioning grant with Fabian Campagne at Cornell. She's also being funded by the Hitchens Foundation's Chronic Fatigue Initiative. She seems to have a talent for taking on interesting studies. She's definitely someone to keep an eye on.

    Metabolomics

    Now she's moving into metabolomics. In the Solve ME/CFS webinar this week Hanson revealed that a small metabolomics study she pieced together using donations had replicated Naviaux's core finding - that ME/CFS is hypometabolic disorder.

    Her study was smaller than Naviaux's: compare the 80 or so patients/controls and 612 metabolites measured in his study to the 32 patients/controls and 361 metabolites in the Hanson pilot study. All the participants n her study were also female and all came from an ME/CFS expert, Dr. Susan Levine, who has been collaborating heavily with Dr. Hanson.

    Comparison-Hanson-Naviaux.jpg
    Naviaux noted that the field is moving so quickly that it lacks standardization and this study showed it. The Hanson team used a different kind of mass spectrometer, and handled the samples differently. In fact, the way Hanson was talking, it sounded like everything was done differently in the Hanson study.

    Nevertheless, Hanson's core findings were strikingly similar to Naviaux's. She found an almost across the board reduction in metabolite levels; fully eighty-eight percent of the metabolites in the ME/CFS patients were reduced (compared to 84% in Naviaux's study.)

    Some similar pathways (phospholipids, purines, proline, fatty acid metabolism) showed up and others did not. The dramatic sphingolipid reductions Naviaux found, for instance, did not show up in the Hanson study, and Hanson found several pathways that did not show up in the Naviaux study.

    Hanson suggested that the completely different methods used as well as the different geographic region the patients hailed from could explain the differences found. Whatever the differences found, the core finding of a distinct hypometabolism in chronic fatigue syndrome (ME/CFS) clearly excited Hanson and she stated:
    Hanson's metabolomic money is gone, but she's applying for an NIH grant. Scoring a big ROI grant - say $3,000,000 over several years - would, of course, be a major step forward for metabolomic research in ME/CFS.

    How to Fit Many Symptoms into One Core Pathology ...

    With the Chronic Fatigue Initiative's help, Hanson has also been studying mitochondrial genetics. Naviaux has stated that people with ME/CFCS do not have a genetic mitochondrial disease, and Hanson's results backed that assertion up; in fact, none of the almost 200 patients tested had anything suggesting an inherited mitochondrial condition. She did, however, find evidence - as Ron Davis has suggested - that genetic polymorphisms could be producing different symptoms in different ME/CFS patients.

    Maureen Hanson's Solve ME/CFS Initiative Webinar

    One altered mitochondrial DNA gene, for instance, appeared to be associated with gut symptoms; another was correlated with chemical sensitivity - a problem that gets almost no research attention - but can be terribly impactful. (Dr. Naviaux believes, interestingly enough, that low energy states lend themselves to hypersensitivity reactions. )Hanson's study suggested genetic differences in the mitochondria could result in widely varying symptoms in ME/CFS. She noted though, that much, much larger studies are needed to validate her findings.

    Hanson is not by any means done with the mitochondria; she is also examining the mitochondrial functioning of NK, T and B cells. The poor functioning of NK cells is one of the most consistently found immune abnormalities in ME/CFS, but problems with T-cell functioning have also been found, and reports of poorly functioning B-cells have shown up as well.

    Could the immune problems in ME/CFS be caused by a hypo-metabolic or under-energized immune system? Hanson will use an Agilent device to determine if problems with glyoclysis - the energy pathway that releases ATP and ATP through the conversion of glucose - are sending immune cells into a somnolent state.

    Hanson then went on talk about her recent gut findings which included a reduction (another reduction) in diversity and abundance of microbial species in ME/CFS. She also suggested that the reduction in microbial diversity seen in an ill twin might be associated with that twins reduced aerobic capacity.

    A New Chronic Fatigue Syndrome (ME/CFS) Center

    In some very good news Hanson announced that the Dean at Cornell has allowed Dr. Hanson to create a new ME/CFS research center called the "Center for Enervating NeuroImmune Disease" (CEND). (Enervating means feeling weak and lacking in energy). The Center will collaborate with Betsy Keller at Ithaca College. It contains three researchers, involves eight labs which have or are applying for an ME/CFS grant, and is working with no less than five physicians - and Hanson hopes it will grow significantly.

    The fact that Hanson felt it was time to create a formal center for ME/CFS at Cornell, plus her ability to hit the ground running with a strong staff is very encouraging particularly at Cornell - which has a top ranked Medical School. The new Center will surely be a strong candidate for the projected NIH research consortium.

    Maureen Hanson is clearly the kind of researcher we've been looking for and hope to get more of. She's very committed, she can get grants, she's daring enough to start an ME/CFS research center and she clearly works well with others.

    Some ME/CFS Metabolomic / Metabolic Studies Coming Up

    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 studycomparing 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.)
    The Bateman-Horne Study



    Depression - Sometimes a Metabolic Disorder?

    ME/CFS might not be the only disease which may get turned around by metabolomics. Let's take a quick look at a metabolomic study that could turn the medical profession's conception of depression - a disease that's often been confused with ME/CFS by doctors - upside down.

    The potential breakthrough started, as many breakthroughs do, with one patient. As reported in the Pittsburg Post-Gazette, frustrated doctors who had run out of options with a treatment resistant young man with suicidal depression, turned to a biochemical geneticist for help.

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    The geneticist suggested doing a metabolic analysis of the young mans cerebral spinal fluid. That analysis turned the his life around. After finding that he had deficient levels of a protein called tetrahydrobiopterin, or BH4, they began treating him with a substance called sapropterin. He was able to recover, return to school and is now working in his chosen field.

    After getting the same results in five other treatment resistant depressed patients, the group began a larger study looking at hundreds of metabolites in the spinal fluid of 33 patients. About two thirds of them displayed significant metabolic abnormalities; of those more than half (12/21) had the same cerebral folate deficiency found in the young man. All showed improvements including reductions in suicidal thoughts on a high dose regimen of folinic acid.

    For some young people on the protocol the improvements have been dramatic. The parents of one 13 year stated that within a month of taking the folinic acid, “we felt like we had our Ben back."

    This isn't to say that all the patients had that kind of result, but it does indicate the power of this technology to uncover new insights that can lead to dramatic improvements even in seemingly intractable diseases like treatment resistant depression (and who knows...perhaps ME/CFS.)

    What would, one wonders, a metabolomic analysis of ME/CFS patients cerebral spinal fluid find?
    • Next up - the McGregor/ Armstrong Australian Metabolic Studies
     
    Last edited: Sep 5, 2016
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  2. Hello!

    Hello! Well-Known Member

    What do you know about Nath's metabolic chamber study? Is it just a relatively crude look at respiration, metabolic rate, etc., or will they also be looking at the more modern metabalomic features of research subjects?
     
  3. weyland

    weyland Well-Known Member

    I had wondered about this, she seems so motivated. We keep getting "lucky" with amazing scientists with sick family members.

    Don't forget about the Bateman/Watanabe study.
     
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  4. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    I have no idea except that Nath said it is very fine-tuned and can find out all sorts of stuff. I believe that the chamber was created many years ago but must have been upgraded significantly for him to say that. I would love to learn more about it.
     
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  5. Hello!

    Hello! Well-Known Member

    We are LUCKY!

    So that bring the count up to at least 8 studies going on!
     
  6. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Whoa! How could I miss that? I also added the Lipkin/Hornig gut microbiome/blood study that is seeking to merge microbiome findings with metabolomics findings in the blood.
     
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  7. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    ME/CFS is clearly it for her - a full time occupation - what a great thing for us! I am soooo glad to hear that another formal center of ME/CFS studies has been created - and in a major University. That is great news indeed.
     
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  8. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    I added the metabolomics depression stuff later - if you haven't read that check it out - pretty spectacular stuff= shows how powerful metabolomics can be.
     
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  9. Hello!

    Hello! Well-Known Member

    I hope this means the results of depressed people are vastly different from those with ME/CFS.
     
  10. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    I think it's very different. All these people needed was one substance (high dose folinic acid); they had a core abnormality that was easily treated; neither Naviaux or Hanson suggest that that is so in ME/CFS or that high-dose folinic acid will cure it. If he had found that he would have said so..how easy that out be.... It just shows how metabolomics can put an entirely new slant on a disease.

    Plus note that that young man and other others didn't have "depression" as we know it; i.e. ap psychological disorder - they had metabolic abnormality.

    The study shows how these metabolic problems can even affect our mood.
     
    Last edited: Sep 4, 2016
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  11. Remy

    Remy Administrator

    So does high dose folinic acid correct a BH4 deficiency better than giving BH4/sapropterin directly like they did with the first patient?

    Or is BH4 deficiency different than the central folate deficiency found in other patients?
     
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  12. fdotx

    fdotx Well-Known Member

  13. Hello!

    Hello! Well-Known Member

  14. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

  15. Kathy Bungard

    Kathy Bungard Member

    I guess after decades of 'media abuse' it isn't surprising that Newsweek took great news and made it a footnote - in my estimation at least - and had to first stress a couple of times that it has been considered a 'psychological' problem instead of a 'real' illness for many years. Yes, thanks to the likes of Newsweek.

    Sorry, but silly me, I had hoped for more.
     
  16. GG

    GG Well-Known Member

    Pretty good article. Although they write CFS then CFA in this paragraph/description. Duh!

    "According to estimates, as many as 2.5 million Americans are believed to have CFS, which mostly affects women in their 30s to 50s. CFA has eight official signs and symptoms, including the central symptom of severe fatigue."

    GG
     
  17. Simone

    Simone Member

    Thanks for this summary, Cort. It is very encouraging to see some overlap in the findings of these studies. I'm glad to hear that you will be also looking at the Australian metabolomics studies too. I think there are some overlaps there also. Exciting times!
     
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  18. Issie

    Issie Well-Known Member

    My understanding is its different. I have MTHFR mutation and BH4 mutation along with others including CBS. They are in a different place in the methylation cycle and different genes are involved. MTHFR has to do with folate. CBS and BH4 can both cause issues with high ammonia. BH4 can affect many neurotransmitters.

    I'm still learning. It's pretty complex, but fascinating.

    Issie
     
  19. Merida

    Merida Well-Known Member

    Very interesting info. Realized that I have so called Metabolic Syndrome. I have written a lot about congenital structural differences - both me and my daughter have spina bifida occulta - just a small missing section of L5 vetebra. Nevertheless, this is considered as a minor neural tube defect by experts. There are many minor congenital anomalies associated with SBO.

    So, I am wondering if the basis of the congenital structural defects is indeed due to a metabolic defect???
     
  20. Snow Leopard

    Snow Leopard Active Member

    Given the major studies being done on this, a meta analysis on the 5+ studies mentioned (albeit in a few years time) will be very interesting.
     
    Manganus likes this.
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