In his response to the NIH's request for Information on ME/CFS Ron Davis called for a massive effort to understand the molecular roots of ME/CFS. This effort would require the NIH to fund studies focused on developing hypotheses instead of answering them. It would result in new ways to analyse proteins, cells and data. Researchers would develop new ways to collaborate. In effect, Davis is trying to usher in a new approach to researching diseases and producing treatments. He argues that such an approach would benefit many. (The full text is below)
An Overview
The Stanford Chronic Fatigue Syndrome Research Center (this is the Davis Stanford Center not Montoya Stanford center) is focused on producing not just a diagnostic biomarker but a molecular diagnostic biomarker; that is, it is focused one finding the shakers and movers in ME/CFS at the cellular level.
A Parkinson's Connection?
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[/fright]It was fascinating that Davis has found transcriptomic (gene), and metabolic (breakdown products of the cell) overlaps with Parkinson's Disease. Parkinson's, in fact, was the only other disease directly mentioned in connection with ME/CFS. It's hard to know how much to read into that mention, but the possible connections between the two diseases - which until recently have hardly ever been mentioned together - are intriguing. Both could be classified as movement disorders, both involve the basal ganglia, both appear to feature reductions in dopamine and inflammation probably plays a major role in both.
From a funding and research perspective, getting ME/CFS allied with Parkinson's - a major neurodegenerative disease - would, of course, be quite helpful.
A Parkinson's - ME/CFS connection could be the kind of surprise we get as researchers dig deeper into the molecular underpinnings of ME/CFS.
More Host Response Than Infection
Davis doesn't appear to put as much faith in the idea that an active infection is causing ME/CFS, as he does that an infection or other stressor probably triggers a more or less system-wide "hypometabolic" or low energy state. (One wonders if Nath's metabolic chamber is going to pick up that hypometabolism.) A system-wide hypometabolic state could explain one of the conundrums in ME/CFS - how so many different systems could be affected.
Davis suggests that ME/CFS has a strong genetic/environmental component. It may be that the genetic factors that underpin this disease get expressed only under certain circumstances such as during an infection or some other trauma. Absent those circumstances, ME/CFS never appears.
Davis noted that even mitochondria diseases - which are largely genetically determined - may remain unmasked until an infectious event occurs. This underscores Davis's belief that the host response to infection is the key, not necessarily the infection itself.
A New Approach To Disease
Davis acknowledges that ME/CFS is likely a very heterogeneous disease but asserts that the way to understanding that heterogeneity is for research efforts to get even more precise. Given our ability now to effectively assess astounding amounts of data, he believes that researchers should engage in massive molecular profiling studies that use new advanced computational techniques to pluck out the heterogeneity present.
How to get those exploratory studies, funded, though, given the NIH's penchant for hypothesis driven studies? Have the NIH produce more "open" RFA's that explicitly call for studies to generate hypotheses. (If the NIH wants a hypothesis driven study the hypothesis could be "We hypothesize that this study will allow us to generate valid hypotheses regarding ME/CFS
)
Davis also wants the NIH to create a collaborative mechanism that allows researchers across the world to share data. To that end innovative new computational techniques that allow researchers to share and analyse data across multiple databases should be developed. (With his Harvard/Stanford connection Davis has already enrolled researchers in developing new ways to analyse the enormous amounts of data the OMF's project is creating.)
In fact, Davis believes that chronic fatigue syndrome with all its complexity offers the opportunity for the medical field to develop new ways to study complex diseases.
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[/fleft](Despite its small size the ME/CFS research field has been an incubator of new techniques. Suzanne Vernon produced one of the first attempts ever to merge clinical, genomic and lab data while at the CDC. Gordon Broderick is doing cutting edge modeling and computational analyses at the Institute for Neuro-Immune Medicine. In order to test treatments more quickly Jarred Younger wants to produce a way to fast-track trials at the Neuroinflammation, Pain and Fatigue Laboratory.)
Davis wants to develop better and more sensitive ways to characterize molecular and cellular data and new computational methods to analyze them. He believes the techniques developed to do that could provide breakthroughs in other diseases.
There's something to being in on the expansion of a field that lends itself to creativity. Because ME/CFS hasn't been well studied it hasn't been captured by one hypothesis or one field of thought. Researchers know that they don't know and they know they need to develop ways to learn as quickly and comprehensively as possible. Developing ways to more or less quickly produce well-founded hypotheses may be the main gift the ME/CFS field can, at this point, provide for other diseases.
Interestingly, Davis emphasized the need for long term studies - something that has rarely if ever happened - but which the Center for Infection and Immunity is now featuring. He closed by making a plea for an open and collaborative effort that brings together researchers of all kinds to solve the many questions facing ME/CFS.
The Full Text is Below
An Overview
The Stanford Chronic Fatigue Syndrome Research Center (this is the Davis Stanford Center not Montoya Stanford center) is focused on producing not just a diagnostic biomarker but a molecular diagnostic biomarker; that is, it is focused one finding the shakers and movers in ME/CFS at the cellular level.
A Parkinson's Connection?
[fright]
From a funding and research perspective, getting ME/CFS allied with Parkinson's - a major neurodegenerative disease - would, of course, be quite helpful.
A Parkinson's - ME/CFS connection could be the kind of surprise we get as researchers dig deeper into the molecular underpinnings of ME/CFS.
More Host Response Than Infection
Davis doesn't appear to put as much faith in the idea that an active infection is causing ME/CFS, as he does that an infection or other stressor probably triggers a more or less system-wide "hypometabolic" or low energy state. (One wonders if Nath's metabolic chamber is going to pick up that hypometabolism.) A system-wide hypometabolic state could explain one of the conundrums in ME/CFS - how so many different systems could be affected.
Davis suggests that ME/CFS has a strong genetic/environmental component. It may be that the genetic factors that underpin this disease get expressed only under certain circumstances such as during an infection or some other trauma. Absent those circumstances, ME/CFS never appears.
Davis noted that even mitochondria diseases - which are largely genetically determined - may remain unmasked until an infectious event occurs. This underscores Davis's belief that the host response to infection is the key, not necessarily the infection itself.
A New Approach To Disease
Davis acknowledges that ME/CFS is likely a very heterogeneous disease but asserts that the way to understanding that heterogeneity is for research efforts to get even more precise. Given our ability now to effectively assess astounding amounts of data, he believes that researchers should engage in massive molecular profiling studies that use new advanced computational techniques to pluck out the heterogeneity present.
How to get those exploratory studies, funded, though, given the NIH's penchant for hypothesis driven studies? Have the NIH produce more "open" RFA's that explicitly call for studies to generate hypotheses. (If the NIH wants a hypothesis driven study the hypothesis could be "We hypothesize that this study will allow us to generate valid hypotheses regarding ME/CFS
)Davis also wants the NIH to create a collaborative mechanism that allows researchers across the world to share data. To that end innovative new computational techniques that allow researchers to share and analyse data across multiple databases should be developed. (With his Harvard/Stanford connection Davis has already enrolled researchers in developing new ways to analyse the enormous amounts of data the OMF's project is creating.)
In fact, Davis believes that chronic fatigue syndrome with all its complexity offers the opportunity for the medical field to develop new ways to study complex diseases.
[fleft]
Davis wants to develop better and more sensitive ways to characterize molecular and cellular data and new computational methods to analyze them. He believes the techniques developed to do that could provide breakthroughs in other diseases.
There's something to being in on the expansion of a field that lends itself to creativity. Because ME/CFS hasn't been well studied it hasn't been captured by one hypothesis or one field of thought. Researchers know that they don't know and they know they need to develop ways to learn as quickly and comprehensively as possible. Developing ways to more or less quickly produce well-founded hypotheses may be the main gift the ME/CFS field can, at this point, provide for other diseases.
Interestingly, Davis emphasized the need for long term studies - something that has rarely if ever happened - but which the Center for Infection and Immunity is now featuring. He closed by making a plea for an open and collaborative effort that brings together researchers of all kinds to solve the many questions facing ME/CFS.
The Full Text is Below
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