August 24, 2010

Study Links Chronic Fatigue to Virus Class

By DAVID TULLER Published: August 23, 2010

When the journal Science published an attention-grabbing study last fall linking chronic fatigue syndrome to a recently discovered retrovirus, many experts remained skeptical — especially after four other studies found no such association.

Now a second research team has reported a link between the fatigue syndrome and the same class of virus, a category known as MRV-related viruses. In a paper published Monday by The Proceedings of the National Academy of Sciences, scientists found gene sequences from several MRV-related viruses in blood cells from 32 out of 37 chronic-fatigue patients but only 3 of 44 healthy ones.

The researchers did not find XMRV, the specific retrovirus identified in patients last fall. But by confirming the presence of a cluster of genetically similar viruses, the new study represents a significant advance, experts and advocates say.

“I think it settles the issue of whether the initial report was real or not,” said K. Kimberly McCleary, president of the CFIDS Association of America, the leading organization for people with chronic fatigue syndrome.

Leonard A. Jason, a professor of psychology at DePaul University and a leading researcher on the syndrome, agreed. “This class of retroviruses is probably going to be an important piece of the puzzle,” he said.

Chronic fatigue syndrome, estimated to afflict at least one million Americans, has no known cause and no accepted diagnostic tests, although patients show signs of immunological, neurological and endocrinological abnormalities. Besides profound exhaustion, symptoms include sleep disorders, cognitive problems, muscle and joint pain, sore throat and headaches.

The new paper, by researchers from the National Institutes of Health, the Food and Drug Administration and Harvard Medical School, was accepted for publication in May. Social networks and online communities soon learned the general findings and were eagerly awaiting the paper.

But in July, researchers from another federal agency, the Centers for Disease Control and Prevention, published a study finding no XMRV or other MRV-related viruses in patients with the syndrome. News of the conflicting findings had led the Proceedings editors and the authors of the new paper to delay publication for further review, and some patients expressed alarm that important scientific information might be suppressed.

People with a diagnosis of chronic fatigue syndrome are used to hearing scientists, doctors, employers, friends and family members dismiss the condition as psychosomatic or related to stress or trauma, despite evidence that it is often touched off by an acute viral illness. Many were ecstatic at news that the second study was being published.

“We’re really hoping this will blow the lid off,” said Mary Schweitzer, a historian who has written and spoken about having the illness. “Patients are hopeful that now the disease itself might be treated seriously, that they’ll be treated seriously, and that there might be some solution.”

The senior author of the new paper, Dr. Harvey J. Alter, an infectious-disease expert at the National Institutes of Health, said he was well aware of the intense interest in his findings but had been unable to respond publicly.

“I was sympathetic to the desire of people to know, and it was difficult because we didn’t feel we could communicate with the patient community directly until the paper was published,” he said.

Retroviruses, including H.I.V., store their genetic code as RNA, convert it to DNA and integrate themselves into the host cell’s genome to replicate. At least three antiretroviral drugs used against H.I.V. have been shown in laboratory studies to inhibit XMRV, which has also been associated with prostate cancer.

Some chronic fatigue patients are already trying H.I.V. medications prescribed “off label.” One patient, Dr. Jamie Deckoff-Jones, a physician in Santa Fe, N.M., has been keeping a popular blog about her improving health while taking antiretrovirals prescribed by her doctor. “I think the sickest patients have the right to try the drugs,” she commented in an e-mail.

Dr. Alter was quick to note that “it’s not at all proven” that a retrovirus causes chronic fatigue syndrome. Instead, such an infection could result from underlying problems with the immune system.

Moreover, it remains unclear why only two research teams found evidence of retroviruses. One reason could be that different groups used varying testing and detecting methods; federal health officials have organized an effort to standardize the process.

The studies also used different methods of sampling chronic fatigue patients. Many experts and researchers argue that the C.D.C.’s strategy leads to overdiagnosis because it fails to fully distinguish the disease from psychiatric disorders like depression.

Officials with the agency say their methods are sound. William M. Switzer, a microbiologist who was the lead author of the agency’s paper, said of the new research, “These are very intriguing findings that need to be confirmed.”

The findings are sure to raise concerns about the safety of the blood supply. AABB, formerly known as the American Association of Blood Banks, recommended in June that people with the illness be discouraged from donating, pending further study.

“The possibility that these agents might be blood-transmitted and pathogenic in blood recipients warrants extensive research investigations,” Dr. Alter and his co-authors wrote in the new study.

Judy A. Mikovits, the senior author of the Science paper, said she hoped to organize clinical trials of antiretrovirals by the end of the year, noting that they could lead to answers about whether a retrovirus causes the disease as well as to effective treatments. (Dr. Mikovits is director of research at the Whittemore Peterson Institute for Neuro-Immune Disease at the University of Nevada, Reno, which collaborated on the XMRV study with the National Cancer Institute and the Cleveland Clinic.)

Cara Miller, a spokeswoman for Gilead, which makes one of the H.I.V. drugs tested against XMRV, said the company was interested but proceeding cautiously. “We are tracking this evolving field,” she wrote in an e-mail, “and will continue to evaluate future research possibilities.”

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