Tuesday, 18 September 2012

XMRV and chronic fatigue syndrome: the results are in...

Drummer boy @ Wikipedia
Drum roll please maestro.

It's been on the horizon for quite a while. The speculation about what will be found, the teaser announcements pinpointing Tuesday 18th September 2012 as the big day, the excitement was building.

And finally here it is.

The big multi-centre study initiated by the US National Institute of Allergy and Infectious Diseases headed by the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health to once-and-for-all answer the question on many a person's lips:

Is XMRV linked to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)?

And the answer....

Very probably not.

The study by Harvey Alter and colleagues* is open-access and published in the the journal mBio.

OK, a quick recap first. XMRV (xenotropic murine leukemia virus-related virus) was initially suggested to be present in quite a number of cases of Chronic Fatigue Syndrome (CFS). It was followed by lots of media attention including some questions over the blood supply, a not altogether successful line of experimental replication, some pretty strong indications of contamination** affecting results, a backstory like something out of a soap opera, and now the final say-so study headed by Prof. Ian Lipkin, microbe and virus hunter extraordinaire (see this previous post on Sutterella and autism).

The study is open-access for all to see and has been covered by a number of sources so far (here) but a quick summary of the results, bearing in mind my considerable non-expertise in the very complicated world of virology:

  • Blood samples were taken from 147 participants diagnosed with CFS and compared with samples from 146  asymptomatic controls. CFS diagnoses were confirmed by several of the criteria available for describing CFS. Said cases had been ill with CFS for an average of 16 years.
  • Blinded analysis of peripheral blood samples was conducted for the genetic footprints of XMRV and pMLV (polytropic murine leukemia virus). 
  • Results: none of the samples (CFS or controls) showed evidence of XMRV or pMLV. The various labs involved in the trial as well as being pretty meticulous in avoiding any contamination, used both positive and negative controls as part of their analytical methods so knew what to look for.
  • There was a suggestion that nine of samples from each group showed a positive result to XMRV / pMRV reactive antibodies but this result is accompanied by some questions about accuracy and specificity to CFS cases.

What's more to say other than the headline by the NYTimes "Chronic Fatigue Syndrome Back to Square 1". Actually no, I wouldn't agree that we are back to square one. As per the comments from Prof. Lipkin, lessons have been learned and also now some very valuable biological samples from quite a well-defined group of people with CFS are available to science to test other theories as and when they come along (as they inevitably will).

I do have one remaining question for the whole XMRV story as per the results reported by Paolucci and colleagues discussed recently. They reported finding something that looked like XMRV/MLV in two of their patient group with CFS. Do the Lipkin findings then mean that they were wrong? Is yet another scientific retraction on the horizon?

Outside of the science bit, I imagine that quite a few people with CFS/ME will carry a sigh at the publication of these results as again, hopes and dreams of getting to the bottom of this mysterious, unexplained condition take another set-back. For their sake, one can only hope that the XMRV episode will at least stimulate more research interest into CFS/ME as per other US Government departments talking about CFS with drug development in mind. Not forgetting also that there are several areas of research into CFS which seem really quite interesting such as the recent mitochondrial findings and the whole immune functioning area.

OK, that's enough for now. 

I was pondering what song to finish this post with. Something related to the post? Nah, instead something completely unrelated... the Noisettes and That Girl.

Update (18/09/12): The association between XMRV and prostate cancer has also been questioned as per this study by Lee and colleagues (full-text).

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* Alter H et al. A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus. mBio. 2012; 3: e00266-12.

** Stieler K. et al. XMRV induces cell migration, cytokine expression and tumor angiogenesis: are 22Rv1 cells a suitable prostate cancer model? PLoS ONE. 2012; 7: e42321.

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ResearchBlogging.org Harvey J. Alter, Judy A. Mikovits, William M. Switzer, Francis W. Ruscetti, Shyh-Ching Lo, Nancy Klimas, Anthony L. Komaroff, Jose G. Montoya, Lucinda Bateman, Susan Levine, Daniel Peterson, Bruce Levin, Maureen R. Hanson, Afia Genfi, Meera Bhato, HaoQiang Zheng, Richard Wang, Bingjie Li, Guo-Chiuan Hung, Li Ling Lee, Stephen Sameroff, Walid Heneine, John Coffin, Mady Hornigo, & W. Ian Lipkino (2012). A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus mBio : 10.1128/​mBio.00266-12