Meanwhile, other researchers at Emory University/Atlanta Veterans Affairs Medical Center and the University of Utah have been looking for ways to treat XMRV should it turn out to have a causal role in prostate cancer or chronic fatigue syndrome. The team evaluated 45 compounds, mostly drugs approved for the treatment of HIV/AIDS, and found that four of them were able to inhibit XMRV with EC50 values of < 1µM. XMRV replication was studied in both MCF-7 cells (generated from human breast cancer) and LNCaP cells (generated from human prostate cancer). The most effective compounds were two nucleoside reverse transcriptase inhibitors (zidovudine and tenofovir disoproxil fumarate) and two integrase inhibitors (raltegravir and L-000870812). Despite the lack of homology (only 14% identity) between HIV-1 integrase and XMRV integrase, raltegravir showed particularly good activity against XMRV with EC50 values of 0.005µM and 0.03µM in MCF-7 and LNCaP cells respectively (cf 0.001µM for HIV-1 grown in PBMCs). The EC90/EC50 ratio was significantly higher for XMRV grown in MCF-7 cells than for XMRV grown in LNCaP cells or for HIV-1 grown in PBMCs (700, 15 and 9 respectively). Synergy studies were carried out in LNCaP cells: combinations of raltegravir and any of the other three compounds were found to act synergistically.
The authors hope that if XMRV is established as a cause of prostate cancer or CFS, existing HIV treatments may prove to be effective therapies for these conditions.
The study is published in PLoS ONE.