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experts comment on two studies and editorial published in Science on association between XMRV and Chronic Fatigue Syndrome

New studies look at the association between the virus XMRV and chronic fatigue syndrome.

 

Dr Esther Crawley, Consultant Senior Lecturer, University of Bristol, said:

“Children with CFS/ME and their families have been concerned about whether they should have anti-retrovirals or be tested for XMRV since the original paper by Lombardi in 2009. This has caused a lot of distress and anxiety. These papers and the clear direction from Science demonstrating concern will now hopefully lay their worries about infection from an unknown virus to rest.”

 

Prof Myra McClure, Professor of Retrovirology, Imperial College London, said:

“Our group was the first to fail to replicate the findings of Lombardi et al when we published 9 weeks after the appearance of the Science paper that we were unable to find XMRV in CFS patients aqnd stated quite clearly then that we did not believe in the association for the reason that there were obvious flaws in the original paper. Moreover, we know that Retroviruses have a long history of being associated with diseases, but most of these associations have ultimately been disproved. XMRV and CFS is another to be added to the list.

“We were sceptical from the outset as we believed that the high similarity of XMRV to murine endogenous MLVs could cause false positive results, as “XMRV-specific” PCR primers could cross-react with similar related viruses present in mouse DNA. Subsequently, we have shown that XMRV sequences are found only in the presence of contaminating murine DNA. We will be presenting some data at the forthcoming 15th International Conference on Human Retroviruses that explains how this mouse DNA may be contaminating laboratories, which will follow on from the work of Sato et al, who have shown laboratory enzymes harbour murine DNA sequences.

“Although scientists have been convinced for some time now that the association of XMRV with CFS was not real, the two studies in Science are timely and will surely end the story once and for all. When all else has failed, Lombardi et al have fallen back on the argument that no-one had investigated their particular CFS patients. Now Jay Levy has and found them not to have XMRV. This, with all the other negative studies buries the story.

“The other study by Pathak and Coffin hammers in the final nail. By passaging prostate cancer cells through nude mice in the 1990s, these cells picked up an endogenous murine virus resulting from a recombination event between two XMRV-like proviruses, generating replication-competent XMRV. Thus, there is no natural reservoir of XMRV in the human population.

“It also means that any CFS or prostate cancer diagnosed before the 1990s could not have been caused by XMRV, (since the virus did not exist then). Yet, Mikovits found XMRV in the blood of her CFS patients, although this blood was taken after 2000 and about a quarter of these patients had been diagnosed with CFS in the 1980s. Quod erat demonstrandum.”

 

Dr Jonathan Stoye, Head of the Division of Virology at the UK Medical Research Council’s National Institute for Medical Research, said:

“Given the failure of multiple labs to reproduce the detection and isolation of XMRV following the protocols described by Lombardi et al, the recent demonstration of the recombinant origin of XMRV as well as the lack of sequence variation in the various isolates reported by the WPI this action by Science to request the retraction of the paper has seemed inevitable for several weeks.

“I think it is important that the myth that XMRV causes ME/CFS is dispelled as rapidly as possible, not only to prevent people being injected with potentially toxic antiretroviral drugs but also to allow research into the real causes of this condition to resume.”

 

Prof Anthony Cleare, Institute of Psychiatry, King’s College London, said:

“These latest findings follow a swathe of studies that contradicted the initial link between XMRV and CFS. Contamination seems increasingly likely to have occurred in the initial study, hence the unusual step of the Editor-in-Chief of Science in publishing his concerns. I would repeat the advice to patients with CFS not to take any potentially harmful treatments such as anti-viral drugs based on what seems now very unlikely to be a cause of their condition.”

 

Prof Tim Peto, Consultant Infectious Diseases Physician, University of Oxford, said:

“The original work linking XMRV to chronic fatigue syndrome was a surprise to many of us but was widely picked up in the media and by the public. Experts have had doubt for some time about the validity of this work, although it was never clear what it was that caused the outcome of the original paper to be wrong. This work tells us what went wrong and there is now no longer any room to argue that XMRV causes chronic fatigue syndrome.

“This is unbelievably careful work to show what was wrong with the original study – why the virus was found in the samples. I am impressed by the strength and quality of this work that has been carried out to the highest possible standard.

“Nobody wants to waste their time on a false trail – we can now pursue other directions of research to find out more about what causes the illness and how best to treat it.”

 

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