XMRV Link to CFS Accelerates Scientific and Media Interest
In the Oct. 8, 2009 issue of Science Express, researchers at the Whittemore Peterson Institute (WPI), the Cleveland Clinic and the National Cancer Institute (NCI) report that 67% of 101 chronic fatigue syndrome (CFS) patients tested positive for infection with xenotropic murine retrovirus (XMRV), a gammaretrovirus associated with a subset of prostate cancer. Only 3.7% of 218 healthy subjects tested were positive for the virus. Read the joint press release.
These important results provide evidence of the association of at least a subset of CFS cases with retroviruses, a hypothesis formed in the mid-1980s and pursued by several independent research groups. XMRV was discovered in 2009 in a subset of prostate cancer patients tumor cells.
The authors raise questions about this discovery at the end of the article, including Is XMRV infection a causal factor in the pathogenesis of CFS or a passenger virus in the immunosuppressed CFS patient population? This question and others warrant additional investigation and the replication of this studys findings in other patient cohorts has generated new interest in CFS by many research groups. Two studies reporting negative results have been published in Jan. and Feb. by researchers in the U.K. A third negative study was reported by Dutch researchers on Feb.25. Several new XMRV-related studies were presented at the 2010 Conference on Retroviruses and Opportunistic Infections on Feb. 19, 2010 and others have been published in peer-reviewed journals. Comments on the initial report in Science, along with a response from two of the 13 authors of that paper appeared in the May 14, 2010 issue of Science. A fourth negative study from researchers at the Centers for Disease Control & Prevention (U.S.), Robert Koch Institute (Germany) and Blood Systems Research Institute (U.S.) was reported in Retrovirology on July 1, 2010.
In the June 1, 2010 issue of Nature Reviews Urology, Robert Silverman and colleagues at the Cleveland Clinic published a detailed review of the data on XMRV in prostate cancer and CFS. They suggest that, In CFS, XMRV infection of blood cells could trigger immune suppression leading to secondary infections and effects on the central nervous system. (See figure at right.) Their final paragraph summarizes the current state of CFS studies and implications:
The presence of XMRV in CFS is a more recent finding that awaits independent confirmation and validation in multiple laboratories; ideally in blinded studies. However, if a role for XMRV in CFS is established it could have far-reaching implications. In particular, while XMRV has not been proven to cause disease, if a link is established with prostate cancer, CFS, or other disease, more effective and more specific diagnostics, treatments and prevention (that is, vaccination) all remain distinct possibilities. Finally, if sufficient risk exists of disease caused by XMRV infection, screening of donated blood to prevent transmission through transfusion might eventually be deemed prudent and necessary.
The U.S. Department of Health and Human Services is supporting studies to assess the potential risks to the blood supply that will standardize tests for XMRV. Canada changed its policy for blood donors with a history or current diagnosis of CFS on April 7, 2010, and Australia's Red Cross announced on April 28 that it will indefinitely defer donors with a history or current diagnosis of CFS. New Zealand is reported to be following Canada's guidelines. An update on U.S. blood safety studies was provided at the May 10, 2010 meeting of the CFS Advisory Committee and the committee recommended to the Secretary of Health that, Given the concerns for patient health, that the Secretary ask the government and non-government organizations responsible for the US blood supply to indefinitely defer individuals with a current or past history of CFS from donating blood and that a screening question about CFS be asked of all donors. The CFIDS Association has long advised patients against donating blood or organs; in its XMRV Q&A, the National Cancer Institute also advises against CFS patients donating blood.
On June 18, 2010, the AABB issued a bulletin to its membership advising that CFS patients be discouraged from donating blood. The bulletin included information about CFS and a poster for use in blood donation centers. The CFIDS Association issued a statement that day commending AABBs action.
Publication of several XMRV studies of CFS patients is anticipated, with papers pending from groups at the National Institutes of Health/Food and Drug Administration (NIH/FDA), Tufts University (presented at Invest in ME conference in London), Institut de recherches cliniques de Montral (presented at the Cold Spring Harbor Laboratorys Conference on Retroviruses) and other institutions. Journals employ different review processes and the length of time from submitting a manuscript to publication can vary greatly. Journals also have different rules about pre-publication release of data into the media; unofficial reports sometimes jeopardize papers in press. Data will have much more impact if it gets into high-impact journals, so we urge patience until published reports are officially released. The study pending from NIH/FDA attracted a lot of attention in June after news of its conclusions was leaked by a Netherlands news agency. The researchers have conducted additional experiments as requested by the reviewers and their paper is expected to be published in the Proceedings of the National Academy of Sciences within weeks.
Speaking at a meeting at Tulane University on June 18, 2010*, Dr. Frank Ruscetti, one of the authors of the Science paper, listed the following "reasons for the lack of detection of XMRV" in his presentation:
Greater sequence diversity than originally believed
In vivo reservoir(s) of viral replication not identified
World wide distribution scattered like HTLV-I
Patient selection and methods applied vary widely
Research on XMRV in CFS continues at other institutions and a new NIH grant was awarded in May 2010 to a group at Cornell University that will study patients who became ill in Lyndonville, New York in the mid-1980s as children.
This summer, the Department of Health and Human Services Blood XMRV Scientific Research Working Group, of which Association scientific director Suzanne D. Vernon, PhD is a member, will analyze results of analytical samples of XMRV processed by six laboratories (including the Whittemore Peterson Institute) to standardize assay results. Association CEO Kim McCleary is a member of the AABB's XMRV Task Force that formed the recommendations regarding blood donation. That group meets regularly and will continue to do so.
There is currently no FDA-approved test available for XMRV and studies of antiviral and antiretroviral treatments must be conducted to test their efficacy against XMRV infection and their safety in XMRV-positive patients.
The CFIDS Association of America congratulates Dr. Judy Mikovits and her team at the Whittemore Peterson Institute and their collaborators at the Cleveland Clinic and NCI for this landmark discovery. The findings themselves and publication of them in a journal of the stature and circulation of Science is a highly significant contribution to the field. Their study and the high-profile publication are important validation of the reality and seriousness of CFS and those who suffer and have been stigmatized too long.