In what may prove to be the first major breakthrough in the fight against the mysterious disorder known as “chronic fatigue syndrome,” researchers reported today that they have found traces of a virus in the majority of patients with the disease.
The same virus has previously been identified in at least a quarter of prostate tumors, particularly those that are very aggressive, and has also been linked to certain types of cancers of the blood.
It remains possible that the virus, known as xenotropic murine leukemia virus-related virus, or XMVR, is a passenger virus that infects patients whose immune systems have been suppressed by other causes.
But the new findings were sufficiently alarming that the National Cancer Institute called together a group of experts in August to consider its potential effect on public health.
“We are in the very early days,” said Stuart LeGrice, director of the National Cancer Institute’s Center of Excellence in HIV/AIDS and Cancer Virology, who organized the meeting but was not involved in the new study. “The data need to be confirmed and repeated. … We need to know that it is a cause and not just a passenger. In a sense, we are at the same stage as we were when HIV was first discovered. Hopefully, we can take advantage of what we learned from working with it.”
LeGrice emphasized, however, that traces of the virus have been found in blood samples preserved for 25 years.
“This is not associated with a new and spreading disease. We are not on the verge of an epidemic,” he emphasized.
Chronic fatigue syndrome, which affects at least 1 million Americans and more than 17 million people worldwide, is characterized by debilitating fatigue, chronic pain and depression, as well as other symptoms.
Many doctors have argued that it is not a real disorder because there have previously been no biochemical markers that characterize it. The only effective treatments are behavioral changes and antidepressants, and they are of limited benefit.
CFS has been theoretically linked to a variety of other viruses, including Epstein-Barr virus and human herpesvirus-6, but none have been found in a significant proportion of patients. Today’s findings could explain why. Like HIV, which causes a constellation of symptoms, XMRV is a retrovirus, and retroviruses are known to suppress the immune system, making it easier for other viruses to establish themselves in a human body.
Dr. William Reeves, who heads CFS research at the Centers for Disease Control and Prevention, cautioned against racing to any conclusions based on the new findings, even though he characterized them as promising.
“It is almost unheard of to find an association of this magnitude in any study of an infectious agent and a well-defined disease, much less an (ill-defined) illness like chronic fatigue syndrome,” he said.
It is extremely difficult to prove causation with a ubiquitous virus like XMRV, and it “is even more difficult in the case of CFS, which represents a clinically and epidemiologically complex illness,” he added.
The new study was organized by Judy Mikovits, director of research at the Whittemore Peterson Institute, a CFS-oriented facility on the campus of the University of Nevada, Reno.
Others in the study included cancer biologist Robert Silverman of the Cleveland Clinic Research Institute, who discovered XMRV three years ago and was the first to link it to prostate cancer, and Francis Ruschetti of the laboratory of experimental immunology at NCI, where Mikovits worked for 20 years before moving west.
The team reported in the online version of the journal Science that they found the virus in 68 of 101 blood samples from patients with CFS, but in only eight of 218 healthy patients.
Mikovits said they have also found antibodies against the virus in 95 percent of the CFS patients.
Experts noted that no test is perfect at identifying all cases of an infection, and the antibody tests Mikovits used are still being refined.
“My gut feeling is it’s not a carrier virus,” she said. “It’s a human retrovirus, just like HIV, which is why all those other pathogens are not able to be controlled.”
The close association with CFS is important, she added, because “never before has there even been a biomarker in this disease.”
The team concluded that the virus is not transmitted through the air. It is found in saliva and blood products, and the implication is that it is sexually transmitted, “but that has not been proven,” LeGrice said.
Unfortunately, Reeves said, the major flaw of the study is that there is not enough information about how both the CFS and healthy subjects were selected to rule out any bias in choosing them, which could have influenced the results.
The fact that the virus is found in nearly 4 percent of healthy people is also of concern, wrote molecular biologist John Coffin of Tufts University in an editorial accompanying the report. That suggests that there could be at least 10 million Americans who are infected and have not developed any symptoms.
Right now, the priority is to develop better screening tests for the infection and conduct larger epidemiological studies, LeGrice said.
Abbott Laboratories is already working on an assay and may present results in November. NCI is also developing an RNA-based assay and the institute may begin growing the virus to provide uniform samples to researchers.
Mikovits, meanwhile, is charging ahead with potential treatments. The reverse transcriptase enzyme in XMVR — which converts the viral RNA into DNA that can be integrated into the infected cell’s genome — is virtually identical to that of HIV, and she hopes that drugs designed for the latter would work on the former.
Mikovits also hopes to begin clinical trials after the first of the year if she can find funding.