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New Doubts on XMRV as Chronic Fatigue Syndrome Cause

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Updated: 4/07/2012 6:13 pm

June 1, 2011 -- A retrovirus found in the blood samples of some patients with chronic fatigue syndrome likely appeared there as the result of contamination, rather than infection, two new studies show.

Since 2009, when a group of scientists reported finding the retrovirus called XMRV in 67% of patients with chronic fatigue syndrome (CFS) compared to just 4% of people without the condition, scientists around the world have tried to duplicate the results, mostly without success.

At the same time, growing evidence has pointed to the possibility of widespread contamination of lab samples with XMRV, and the new studies lend credence to that theory.

Evidence of Contamination

In the first study, researchers at the University of California at Davis, Tufts University, and the National Cancer Institute traced the ancestry of the XMRV virus and found evidence that it was accidentally created by lab experiments in mice in the 1990s. Tumors grown on the mice were then used to create an experimental cell line and laboratory testing products that likely contaminated other samples.

In the second study, researchers at the University of California at San Francisco, Abbott Laboratories, the Wisconsin Viral Research Group in Milwaukee, and the Open Medicine Institute, in Mountain View, Calif., tested blood samples from 61 CFS patients, including 43 who had previously been told they tested positive for XMRV. After a year, using different methods to look for telltale signs of the virus or viral infection, they reported finding no traces of XMRV.

"It's time to let XMRV die," says Mark A. Wainberg, an expert on retroviruses and professor in the department of medicine, division of experimental medicine at McGill University in Montreal, who was not involved in the research.

The studies may disappoint some patients with chronic fatigue syndrome, who had hoped that the discovery of a retrovirus linked to their condition might one day lead to new treatments or at least definitive tests for the mysterious and often debilitating syndrome. Some patients had even sought antiretroviral drugs, the same class of medications that are used to treat HIV infection, to relieve their symptoms.

Citing the "far-reaching impact" of the 2009 paper, the editors of the journal Science, which published both the original paper and the two new studies that give weight to the contamination theory, have published a "Letter of Concern" and asked the authors of the 2009 paper to retract their research.

Some researchers applauded the journal's decision to question the validity of the paper.

"It's giving a false message to patients who have placed a lot of hope on the fact that they might be infected with XMRV and therefore XMRV might be the cause of their disease and they're going to be able to be treated with antiretrovirals," says Vinay K. Pathak, PhD, chief of the viral mutation section at the National Cancer Institute in Frederick, Md. "It would be nice if it's true, but it's just not reality."

Study Researchers Respond

In a written response, study researcher Judy A. Mikovits, PhD, director of Research at the Whittemore Peterson Institute in Reno, Nev., defended her 2009 paper. She called the journal's expression of concern "premature" and said its publication "would have a disastrous impact on the future of this field of science."

A government-sponsored trial is under way to see if the XMRV virus can be detected in patients with CFS, and researchers pledged that it would go on, even in light of the negative findings of the new studies.

Failure to Replicate Findings

Since the publication of the original paper in 2009, at least 11 groups have tried, and failed, to find XMRV in chronic fatigue patients, while one group found evidence of related viruses called murine leukemia viruses in about 87% CFS patients compared with only about 7% of healthy patients.

Study researcher Jay A. Levy, MD, head of the Laboratory for Tumor and AIDS Virus Research at the University of California at San Francisco, who was one of the first scientists to identify XMRV, says he became suspicious when he noticed how similar the virus appeared to be between samples.

"They were so identical that it did not make sense," Levy says. "When the virus replicates it always changes."

Additionally, he says, studies have shown that XMRV is rapidly deactivated by the body's defenses and doesn't survive for long in blood.

So he approached the same medical practice that tested patients for the original 2009 paper and retested 43 patients who had been told they tested positive for XMRV and 18 more that had a diagnosis of CFS.

Using multiple ways to look for traces of the retrovirus, they found no evidence of its presence in any of the patients they tested.

"We were able to cover everything in the Lombardi paper, and even more so," Levy says. "The evidence does definitely look like contamination."

Levy, who has also studied chronic fatigue syndrome, says he believes it is an autoimmune disease. He thinks something that sets off the immune system in patients with CFS, and that it fails to quiet down after the initial insult, leading to long-term illness.

He says patients with CFS shouldn't be discouraged by the latest findings, which he says amounted to a distraction in the search for a cure.

"Patients have to realize that this doesn't mean, yet again, they aren't going to get any attention. If anything, it puts attention on this syndrome and says, 'Find the real reason. Find the real solution,'" he says.

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