For Wozniak and Itzhaki, the next step is to test whether antiviral drugs like Zovirax and Valtrex, both of which are used to shorten the duration of cold sores, might alleviate or slow the progression of Alzheimer's. The pair is seeking funding for two experiments with antiviral drugs—one testing them on mice, the other testing them on Alzheimer's patients.
"If the treatment is successful, it would stop progression of the disease, rather than just stopping the symptoms," Itzhaki says.
But that funding isn't likely to materialize if the rest of the research community continues to dismiss Itzhaki's theory—or ignore it altogether. When I e-mailed John Trojanowski, M. D., Ph. D., a respected Alzheimer's researcher at the University of Pennsylvania, to find out his take on the connection between Alzheimer's and herpes, he shot back a one-sentence reply: "Do not know of any connection."
When I pressed and asked him to take a look at two of Itzhaki's recent studies, he was equally dismissive. "This is an old story," he said, "so I do not think there is much new news here."
Even those more familiar with the research remain skeptical. "One of the things we see a lot in science is relationships—two things happening together," says Bill Thies, Ph. D., chief medical and scientific officer at the Alzheimer's Association. "But they often turn out to be independent events, or you can't tell which thing is causing which. It could be, for example, that there's something about amyloids that attracts HSV."
Wozniak says that the study he published with Itzhaki—in which the herpes virus caused amyloid accumulation in cells and mice—refutes that criticism. He also dismisses another critique—that he and Itzhaki haven't established the mechanism by which HSV-1 brings about that accumulation. Again, he argues, this study indicates an increase in the enzymes that are responsible for forming amyloid from its precursor protein, called APP.
"Surely, the mechanism is clear: HSV-1 causes an increase in these enzymes, which in turn causes degradation of APP, leading to amyloid formation." He pauses, and then adds wryly, "It's interesting that people raise this criticism when, until our research, no other underlying causes of amyloid production linked to Alzheimer's disease were known."
Itzhaki is more sanguine about the skepticism. "We've seen this before when a virus or bacterium is suggested as the cause for a chronic illness," she says, noting the reticence people had when H. pylori was suggested as a cause of ulcers and when the human papilloma virus was suspected as a cause of cervical cancer. Both are now largely considered medical fact. "And the Alzheimer's establishment is very conservative."
Georgetown's Dr. Federoff agrees that in some ways the theory isn't conventional enough to be embraced by many mainstream Alzheimer's researchers. "Herpes is a common virus, but in this case we're talking about it behaving in an atypical way," he notes. That said, would he like to see further research on the connection between HSV and Alzheimer's? Absolutely.