Four drugs that are used to treat the AIDS virus HIV can also inhibit the replication of xenotropic murine leukemia virus-related virus (XMRV), a mouse virus that has been found in some patients with prostate tumors and chronic fatigue syndrome. Now all researchers have to do is show that XMVR is actually a cause of disease rather than a passenger virus, as most researchers now suspect.
XMRV, a retrovirus that, like HIV, inserts a DNA copy of its RNA genome into the nuclear DNA of its host, was discovered in 2006 by researchers at UC San Francisco and the Cleveland Clinic. It was first found in about a third of tumor tissues from patients with prostate cancer, particularly those with the most aggressive form of the disease. Subsequently, researchers from the Whittemore Peterson Institute for Neuro-Immune Disease in Reno said that they found it in about two-thirds of 101 patients with chronic fatigue syndrome, a mysterious debilitating illness that some doctors think is more psychological than physical. Since then, however, three further studies conducted in Europe have failed to find the virus in any patients with chronic fatigue.
Critics have roasted the European researchers -- charging bias, among other things. One potential problem, advocates of the virus theory argue, is that the European researchers did not use precisely the same assays that the Americans did. In an effort to circumvent this problem, a team led by Dr. John A. Petros, a urologist at the Emory University School of Medicine, developed a new assay for antibodies to XMRV similar to the antibody-based assays used for identifying HIV infection. They reported Monday in the journal Urology that they used the antibody test to detect XMRV in 11 of 40 patients who had undergone a radical prostatectomy, about the same proportion of patients found in other studies. Their results were confirmed by other laboratories using independent assays.
"We cannot as a scientific community begin to answer the basic questions of XMRV transmissions, frequency in the population, association with disease, etc., until we can effectively test for infection," Petros said in a statement.
If the virus can ever be shown to be a cause of prostate cancer or chronic fatigue, Dr. Ila R. Singh of the University of Utah School of Medicine, chemist Raymond F. Schinazi of the Emory University School of Medicine and their colleagues tested four HIV drugs against XMRV grown in cultures of breast cancer and prostate cancer cells. They reported Wednesday in the online journal PLoS One that the four drugs -- raltegravir, Zidovudine, tenofovir and an experimental drug called L-00870812 -- each blocked XMRV replication, but that the drugs were most effective when used in combination. "Our study showed that these drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that highly potent 'cocktail' therapies might inhibit the virus from replicating and spreading," Schinazi said in a statement.
The drugs cannot ethically be tested in prostate cancer and chronic fatigue patients, however, until it is shown that the virus actually causes disease.
-- Thomas H. Maugh II