The patient community has been on a wild ride lately. No, no studies have been published but patients are digging deeper into the studies and coming up with some surprising findings.
Three, er… make that two CFS XMRV validation studies?
After digging deeper into the cohort from the last Dutch study Parvofighter on the Phoenix Rising Forums has uncovered some disquieting facts about them. We knew that they were defined using the Oxford definition – which is not optimal, for sure – but what Parvofighter uncovered appears to go beyond using a poor definition.
The samples from that study were gathered a long time ago – prior to the creation of the standard Fukuda criteria that researchers use today. We’re talking early in the recent history of CFS when things were even foggier than they are today. Nobody knew what CFS really was back then (and they still don’t) but while these patients were clearly ill in significant ways they just don’t look like CFS patients – either back then or now. This is what they looked like.
Seventy-one percent had muscle pain – fine, but only 51% said they had difficulty concentrating; headache, gastrointestinal complaints and dizziness (?) were pretty common (@45%) which is good, but only 43% had sleep disturbances. Both sleep problems and trouble concentrating seem to be present at substantially lower percentages than are usually found in CFS.
Recurrent infections came in at a low 26% and sore throat, one of the cardinal symptoms of the Fukuda definition, is down all the way at 13%. Sore throat isn’t believed to be as common in CFS as was once thought but it’s still far more common than 13% seen this in this cohort. Unfortunately postexertional malaise was not part of the symptom picture at that point and we don’t know about that.
In short, while the group does have some similarities to CFS as we know it, in several significant ways this group does not seem very “CFS’ey” – a fact that could certainly complicate a researchers ability to find XMRV. This was a study that appeared to put the nail in the coffin for XMRV for some researchers but one wonders just how likely it was that it was ever going to find much XMRV. Instead of calling it the third XMRV CFS study maybe we should just call it an XMRV study and leave it at that.
Just a day after Parvofighter cast serious doubt on the Dutch study Kurt raised some questions about the original Science study. In January Dr. Mikovits stated that researchers not culturing their samples first will not find XMRV because of the very low viral loads. This, of course, lead some in the patient community to wonder if the early studies wanted to find a virus.
But a close look at the original Science paper indicated that the WPI neither cultured nor activated their samples before they get their PCR tests. While patients (and others) have been bashing these studies over the head for not following the WPI’s protocol it turns out that, at least in one important area, they were following the WPI’s protocol.
The question we seem to be left with is why it suddenly became necessary to culture the samples first in order to find XMRV? Why was XMRV so easy to find earlier but is so difficult to find now? The first thing that leaps to mind is the makeup of that original patient cohort.
Could they have been so sick that they simply had much higher viral loads then typical patients and once the WPI started testing more typical patients they had more difficulty finding the virus? It stands to mention that VIP Dx – the WPI’s licensed lab – abruptly shut down for a month in January
One suspects that Dr. Vernon’s focus on the makeup of that original is at least partly due to the no-culture/culture shift. Her analysis of the original cohort suggested that of the 32 CFS patient samples she could get information on only 12 tested positive on more than one assay (of four) and a third of those patients had been diagnosed with cancer. All told 13 of the 67 positive patients appeared to have cancer.
The WPI, on the other hand, has said that no patients had lymphoma and that further information wouldn’t shed any light on XMRV and that no further information will be forthcoming. Annette Whittemore has stated the study participants were randomly plucked out of patient samples in the WPI’s repository gathered from doctors across the US.
Kurt has brought forward a possibility that the validation study results thus far are correct and that XMRV is not found in CFS…but something else is. In this scenario XMRV shows up in those original uncultured samples and then disappears in later uncultured samples and then appears to reappear in cultured samples because the culture process itself is bringing something else out patient’s blood that looks very much like XMRV.
This is a kind of ‘ inadvertent but possibly very lucky’ scenario in which WPI researchers do possibly find an important factor in ME/CFS – just not the one they were looking for. It’s all speculation at this point; with a new set of studies reportedly about to be reported on, XMRV is at a fork right now; the path it ends up traveling down is still wreathed in the fogs of the future.
WPI checking itself
It bears mentioning that WPI researchers are still apparently finding ‘XMRV’ in high percentages of CFS samples but in low percentages of healthy control samples. They are also sequencing new strains. There’s also the new antibody test that is reportedly more specific to XMRV than any test before which we believe the WPI is using. These are all checks on the validity of the original finding that the WPI is engaged in – given enough resources at some point the mud will clear. Meanwhile, this has been quite a ride.