A dormant danger: New therapies target a ubiquitous pathogen known as cytomegalovirus

VOLUME 21 | NUMBER 10 | OCTOBER 2015 NATURE MEDICINE The promise of organ and tissue transplantation has become more fully realized in the last two decades. Since 1990, the yearly number of organ transplants in the US has nearly doubled, according to the Virginiabased United Network for Organ Sharing. At the same time, preliminary data from the Center for Blood & Marrow Transplant Research, a collaboration between National Marrow Donor Program and the Medical College of Wisconsin with coordinating centers in Milwaukee and Minneapolis, suggests that stem cell transplants from donors have shot up more than fourfold over the same period. But as transplants increase, so too does the threat from a virus that lurks in the bodies of most people. Cytomegalovirus, or CMV, usually lies dormant, kept in check by the immune system. But when the immune system is suppressed, as it is in transplant recipients who receive drugs with this effect, the virus can reactivate. Moreover, more types of patients are now receiving transplants, says Roy Chemaly, a virologist at the University of Texas MD Anderson Cancer Center in Houston. “We’re becoming a little bit more aggressive in transplanting elderly people, or patients at high risk with relapse of their leukemia,” Chemaly says. “They are more heavily immunosuppressed. That’s why they get into more trouble with infection.” The problem therein is that the type of CMV that infects humans is hard to study and hard to treat. This version of the virus doesn’t infect other species, so there are no good animal models. A few existing drugs can quell active infections because they can stop the replicating form of the virus. But the virus will go dormant and hide, making it seemingly impossible for drugs to expunge it from the body completely. Moreover, the drugs available to treat CMV have dangerous side effects, so doctors must balance the risk from the virus with the risk from the medications themselves. Thankfully, a wealth of new treatments for CMV is on the horizon. At least three drugs against the virus are in late-stage clinical development, each with a promising safety profile, and many companies are working on vaccines. Safer treatments could let doctors treat patients sooner, before the virus can cause harm.