Tuesday, March 22, 2011

Scientists race to find the biological cause for chronic fatigue syndrome

Unlocking Chronic Fatigue Syndrome


As scientists race to find a biological cause for chronic fatigue syndrome, long considered by many doctors to exist in patients' heads, the National Institutes of Health could shed new light on the debate at a major scientific workshop on the disorder.

Researchers at the University of Utah and elsewhere are working to create diagnostic tests, based partly on proteins or other markers that appear to show up in greater quantities in patients with chronic fatigue syndrome. Diagnosing the disorder is difficult, in part because symptoms vary among patients.

Other scientists are trying to understand why other infections, such as mononucleosis, appear to prompt chronic fatigue syndrome in some patients. And in a program at New York's Columbia University, researchers are seeking to identify pathogens that may appear prominently in patients with the disorder. Researchers will be testing "for all those agents that we know affect vertebrates on this globe," says Mady Hornig, who heads the Columbia program.

Chronic fatigue syndrome affects between one million and four million Americans. They suffer from memory and concentration problems, debilitating pain and severe fatigue. Unable to identify a cause, doctors often dismissed these patients as complainers.

Currently, diagnosing chronic fatigue syndrome is largely a process of elimination. Molly J. Billings, 22 years old, first showed symptoms of the disorder in 2004, including headaches, muscle aches, fatigue and weakness. A year later, she could only get around by wheelchair and was bed-bound most of the time. She endured years of tests to rule out other medical explanations for her condition.

"It was horrible to go and not find anything," says Ms. Billings, who lives in Kendall, N.Y. "I want a test that will give me a finite result." Today, her symptoms have shown gradual improvement. She attends classes twice a week at a local community college and is able occasionally to go out with friends.

CFS, also known as ME for myalgic encephalomyelitis, got a boost of attention in 2009 when the journal Science published a study that found the retrovirus XMRV was present in most members of a group of chronic fatigue syndrome patients. The 2009 study divided scientists and led to intense debate about whether the XMRV link is a breakthrough or a result of lab contamination. The study launched a wave of new research.

Anthony Komaroff, a doctor at Harvard Medical School who treats chronic fatigue syndrome patients, was involved in a study that found viruses in the same family as XMRV in his patients. Meanwhile, Brigitte Huber, professor of pathology at Tufts University, was involved in separate work that failed to find XMRV. They are now collaborating on a project that received funding last year to study two viruses in patients with the syndrome.

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Because symptoms of the syndrome tend to wax and wane, the researchers are investigating whether the viruses may be easier to detect when the symptoms are flaring. Dr. Komaroff is taking blood samples from patients when they are feeling relatively well and when their symptoms are pronounced. Dr. Huber will then analyze the blood to see if she can detect higher amounts of these viruses during times when people feel worse.

Jose G. Montoya, a researcher at Stanford University, is searching for possible infectious agents in chronic fatigue syndrome. "If we can find the infectious triggers, we can provide intervention," he says. Dr. Montoya's team enrolled 30 patients with elevated levels of antibodies against Epstein-Barr virus and HHV-6, a herpes virus, in a trial and treated them with valganciclovir, an anti-viral medicine. Dr. Montoya says patients on the drug showed improvement in cognition and fatigue. Researchers are now analyzing the patients' immune proteins to see if there are patterns that will help doctors figure out in advance who will and won't respond to therapy.

A number of efforts are underway to try to develop diagnostic tests. Researchers at the University of Medicine and Dentistry of New Jersey and Pacific Northwest National Laboratory reported recently that they found proteins in the spinal fluid of people with chronic fatigue syndrome that distinguished them from people with Lyme disease, which has some similar symptoms, and healthy controls. The next step is to narrow down the list of proteins to find "the best biomarkers for what is going wrong in the central nervous system," says Steven E. Schutzer of the University of Medicine and Dentistry of New Jersey who helped lead the study.


Nearly 25 years after the "Lyndonville outbreak" of chronic fatigue syndrome, a controversy is brewing among scientists over what causes the disease. A small-town doctor hopes his patients will help provide the answer. WSJ's Jason Bellini reports.

At the University of Utah, researchers are working on what they hope might ultimately lead to a test for chronic fatigue syndrome. Forty-eight patients with the disorder and healthy controls are involved in a trial in which they undergo a 30-minute exercise challenge. Even after moderate exercise, there were increases in gene expression markers in the blood for two days that allowed researchers to distinguish chronic fatigue syndrome patients from healthy controls.

More than 100 scientists, researchers and advocates are expected to gather at the NIH workshop in Bethesda, Md., attending sessions focused on such medical topics as infectious diseases, systems biology, immunology and neurology. By contrast, the last NIH scientific workshop, in 2003, had more emphasis on the psychological aspects of the disease, including stress, insomnia and depression.

Medical history has other examples of diseases that were not taken seriously but later turned out to have biological causes. Multiple sclerosis was once misdiagnosed as hysteria or chronic alcoholism. Today multiple sclerosis is suspected to be an auto-immune disorder. Stomach ulcers were thought to be caused by stress until two Australian scientists proved the bacteria Helicobacter pylori was the cause, work that won the Nobel Prize in 2005.

"The door has been opened by the retrovirus,'' says Mary Schweitzer, a former history professor who has chronic fatigue syndrome and was tapped to serve on the steering committee planning the NIH conference. "Now we want to bring in all the scientific research that is being done."

Write to Amy Dockser Marcus at amy.marcus@wsj.com

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