But what could be the underlying cause of those three phenomena? What is the explanatory hypothesis? I do see in the integration of those studies the suggestion of a hypothesis for related pathological mechanisms, but not one that clarifies the cause of those mechanisms. To me it seems that piecing one's way back from those mechanisms to the root could take a very, very long time; the disease pathologies in ME/CFS are so numerous and complex. I am concerned that with this approach alone we could wind up pulling on strings and getting tangled up for years more. If there was generous national funding for ME/CFS research I might be less worried but given that there is hardly any I would prefer that the focus of our specialist research organizations (at least) be on exploration based on a hypothesis of causation, which I still believe may be simpler than the "Outside-->In" approach. Offhand I can't think up a causation hypothesis that can explain the full biomedical picture of ME/CFS that does not involve pathogens and related immune reactivity. The one study out of six recently funded by the CAA focuses on EBV in vivo, but how does that study tie in with the others to form an explanatory hypothesis or model?
There are countless biological parameters that would be very interesting to investigate, that might also show correlation to the symptoms or severity of ME/CFS, and that might reveal something else that is noticeably wrong with us. But surely the larger percentage of funding should remain related to the pathogen/immune connection, which has always been the most abundant and obvious evidence of a physical disease in patient histories and clinical presentation. Taking that as a starting point (at least by one hypothesis of causation) we can then allow it to direct us where and what to investigate next, given the other noted elements of the clinical picture (PEM, OI, sleep disturbance, allergies and MCS, etc, etc). If, for example, a viral cause or co-cause is posited, one would be more likely to look for the root of ME/CFS hypovolemia or OI in microvascular damage that could be caused by viruses or by excessive cytokine activity than, say, to look for shortages of an enzyme that converts dopamine to norepinephrine (or defects in that enzyme's gene). Both studies would be interesting, but with limited funds (and time, in more ways than one) it makes more sense to pursue studies that flow from a hypothesis with explanatory power.thanksas soon
Their proposed studies, including those not related to XMRV, make good use of limited funds, in my opinion. What they don't do, and likely can't do by themselves, are brain imaging and circulatory studies (which I hope the CAA continues to address and expand upon). The main point, though, is that they wound up finding XMRV because they were focusing on pathogens in the first place. I would say to look that as your working hypotheses (pathogens/immune abnormalities), and let that guide where and how you look next. That doesn't mean you only do research on potential causes, but that your project selection is informed by that hypothesis, even when it focuses on other ME/CFS signs and symptoms (like PEM).
from CBS:
Thanks...and good luck!
The Pathogen question in CFS is dogged by a fundamental problem- there are problems with diagnosis regarding every pathogen that is of interest in CFS. Its kind of remarkable actually; there are lots of pathogens for which diagnostic protocols are well worked out but this is not true for any of the pathogen in CFS that I can think of - we specialize in the controversial pathogens. So when you say, let's just focus on pathogens you're immediately hit with a stumbling block. It sounds like a great idea but its just not very easy.
HHV6- prime candidates for investigation in CFS. There are good tests for HHV6-A and Dr. Peterson has said that, HHV-6 A is the prime focus in CFS but it's possible that HHV-6 B is hat is doing the damage in the central nervous system. HHV6 is a pathogen searching for a disease - something that clearly drive Robert Gallo, a codiscoverer I believe, crazy. At the HHV6 onference he said there's no way HHV-6 could be causing all the disorders that people are attributing to it and that itself is harming the field. He felt the HHV-6 fieldwould never be legitimizeduntil it started focusing on a few disorders. The HHV6 foundation has been working on a diagnostic test for years - they recognize that that is the key element that's missing.
EBV - is not that different. Dr. Montoya believes some diagnostic tests are illuminating that other researchers believe don't tell you anything. Ronald Glazer and Dr. Lerner believe that EBV functioning has been truncated in CFS causing it to spit out proteins that are causing the problem but the rest of the field thinks this is voodoo science and it is not being picked up on. (The CAA is funding his investigation that an aberrant form of EBV is at the heart of CFS. THey are also funding research into HERV's - which they believe could interact with herpesviruses and cause CFS. - two causal pathogen studies)
Enteroviruses - Dr. Chia believes that the diagnostic testing for enteroviruses was simply off -due to no one's fault - for decades. He finally found one diagnostic lab that he felt was doing the right kind of testing. Unfortunately his findings have not spurred on others to look for enteroviruses.
Dubbo - then you have the Dubbo studies suggesting that the infection caused by each of they studied is actually resolved; the pathogen is taken care of but that an overly aggressive immune response somehow turns CFS on.
Another Big Roadblock - Then there's the problem with central nervous system infections. How do you, short of biopsying a person's brain which is illegal or doing an autopsy find them? The pathogensof interest don't even show up in spinal fluid studies very often.
The pathogen field lacks clarity on a very basic level. You have to solve some of the methodological problems before you can really begin to get at them in a credible way. What you have is a nice theory that makes sense but alot of difficulty determining if it's true - particularly if the pathogen is found in the brain.
Cautionary note - If you've followed multiple sclerosis research a bit then you know that the proximate cause of MS - demyelination of the neurons - has been known for decades and they've looked at different pathogens just as long. They've been digging into neurons for decades - and they are still arguing a) if a pathogen causes it and b) if it does which one does......this is after decades of intense effort!
The most convincing evidence of pathogen involvement is probably anecdotal and published reports of patient success when using them. Infortunately we don't have any statistically rigorous, well designed studies on antiviral treatment in CFS - not one. THere's not one placebo-controlled, blinded, good study on antiviral treatment in CFS. So there's really nothing for the academic world outside of CFS to latch onto.
The big pathogen arrays the WPI is using will surely be very helpful as well but they are a pretty recent development and the The WPI has not, I don't think ?, published anything on their pathogen array studies and from what we hear is that they are basically finding herpesviruses - so no real surprises.
We're lucky that XMRV has captured so much interest because you get the idea that maybe they're gonna figure out whether that virus is playing a role.
Pathogens may very well be it but its a tough field. You could argue, XMRV accepted, it would be better to devote one's resources to uncovering the downstream problems because you might have a better chance of affecting them. (Not talking about XMRV here).
I think researchers are pretty smart. I think they are trying to get as close to this disease as they can with the amount of money they have - unfortunately that money is really lacking. If they had more money I think you would see a lot more comprehensive studies that attempt to explain the big picture in CFS.
