The researchers, who were trying to confirm the 2009 study results, say they have failed to find evidence of XMRV infection in some of the same patients who were involved in the original study.
Additionally, some of the authors of the original study announced that they were retracting some of their results after finding evidence of contamination in some of their study samples.
Experts say the new study and partial retraction, which are published in the journal Science, should finally discredit the controversial theory that XMRV causes chronic fatigue syndrome.
"The original findings that led to the concern and the excitement that this is real aren't reproducible," says Michael P. Busch, MD, PhD, professor of laboratory medicine at the University of California at San Francisco and director of the Blood Systems Research Institute.
"I take that as an indication that those results are unreliable," Busch says.
But the authors of the original paper, who were also involved in the new research, have a different interpretation.
They believe XMRV couldn't be found in blood tests because it may hide in the body's tissues, only rarely being picked up in the blood.
They point to recent studies in primates that were experimentally infected with XMRV. The infected monkeys were able to clear the virus from their blood within about a month, but it lingered in other tissues like the spleen and lymph nodes.
"All this study really says is that we can't detect it in the blood reproducibly," says Judy A. Mikovits, PhD, director of research at the Whittemore Peterson Institute in Reno, Nev.
"The interpretation says that it's not there or that it's not a human infection, and there's no data in this study or any other to support that," she says.
Mikovits says she just got a federal grant to continue her work on XMRV. "Clearly things aren't over or they wouldn't be awarding grants for people like us to study this virus and understand those questions," she says.
Testing for XMRV
For the new study, nine laboratories used three different kinds of tests to re-screen 15 people who had once tested positive for XMRV and 15 healthy people who had been found not to carry the virus.
Two of the laboratories involved in the study were also involved in the 2009 paper, which reported finding XMRV in 67% of chronic fatigue syndrome patients compared to just 4% of healthy people, suggesting that the virus could be a cause of the chronic, debilitating condition.
So that the labs could be sure their tests were working correctly, they were also given blood samples that were spiked with small amounts of XMRV.
All the labs were able to find XMRV in these prepared samples, indicating that the testing methods they were using were valid.
But only two of the labs found evidence of mouse retroviruses, including XMRV.
The researchers, Busch says, were unable to detect the virus at higher rates in those CFS patients compared to people that their labs agreed were negative. "I take that as an indication that those results are unreliable."
Time to Move On?
Patient advocates say it's time to refocus research efforts on credible science.
"We share the deep disappointment of many CFS patients and scientists that the initial data did not hold up. Whether you have been diagnosed recently or have been ill for decades, this news comes as a blow to hope for rapid advances in the care available to CFS patients," says Kim McCleary, president & CEO of the CFIDS Association of America, in a prepared statement.
"There are many other solid leads that merit the same rigorous follow-up as XMRV has received over the past two years," McCleary says.
Since the original paper was published in 2009, 17 published studies have tried but failed to confirm the findings of the original report.
Two studies, published earlier this year in Science, found evidence that XMRV had contaminated many of the cell lines and laboratory products used by researchers to test patient samples, skewing the results of several studies that linked the retrovirus to chronic fatigue syndrome and prostate cancer.
Mikovits says the cell line used in her laboratory and in the laboratory of her co-author, Frank W. Ruscetti, of the National Cancer Institute, has never been grown in mice and is thus uncontaminated.
However, samples handled by two of her co-authors in the original paper from 2009 did test positive for contamination. Test results based on those contaminated samples were retracted by co-authors from the findings of the 2009 paper.
In an unsigned statement supporting the partial retraction, the researchers say they now agree that XMRV was unlikely to be a cause of chronic fatigue syndrome.
"We encourage patients to talk with their doctors about approved treatments for symptoms and disease progression," the statement says.
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