Researchers Tested Herpes Drugs for Alzheimer’s. It Backfired

The journey to finding an effective treatment for Alzheimer’s disease seems to have hit another dead end. The latest casualty: medications designed to tackle the viral illness herpes.

Researchers at Columbia University published the disappointing results of their randomized trial this week. Cognition in people with diagnosed herpes and early Alzheimer’s did not improve with antiviral treatment compared to a placebo—in fact, the treatment group actually fared worse. Though the findings don’t necessarily rule out a genuine link between some viral infections and Alzheimer’s, the use of these drugs for treating dementia shouldn’t be encouraged, according to outside experts.

“For persons with symptoms of cognitive impairment, there is no, repeat no, role for antiviral therapy,” David Knopman, a clinical neurologist at the Mayo Clinic not affiliated with the study, told Gizmodo.

The viral hypothesis

Alzheimer’s is the most common form of dementia, affecting over 7 million Americans today.

The disorder is characterized by having high levels of two misfolded proteins in the brain: amyloid beta and tau. But researchers are still unsure about the exact role these proteins play in driving the disease or what triggers the chain of destruction that eventually consumes the brain.

In recent years, some research has suggested that certain viruses and other germs might be one potential cause of Alzheimer’s, or at least an important contributor to the disease—the so-called viral hypothesis of Alzheimer’s. Some studies have found that herpesvirus infections can trigger the build-up of amyloid beta plaques in mice with human-like brain cells, for instance, or that people who die from Alzheimer’s are more likely to have herpesviruses in their brains than people without the condition.

These studies have only provided indirect evidence of a viral connection so far. But if such viruses can cause Alzheimer’s, then it might be possible to prevent or slow its progression by treating a person’s underlying infection. And that’s what these researchers set out to test.

A study failure

The randomized, controlled trial involved 120 participants diagnosed with probable Alzheimer’s or mild cognitive impairment likely to develop into Alzheimer’s. They also tested positive for antibodies to herpes simplex virus type 1 or 2. HSV-1 is the primary cause of cold sores, while HSV-2 most often causes genital herpes, but either type can cause the other.

For 18 months, the participants were randomized to take a daily placebo or valacyclovir (better known by the brand name Valtrex), a standard treatment used to manage HSV and other kinds of herpesvirus infections.

By the study’s end, the treatment group saw a significantly worse progression of cognitive decline compared to the placebo. Based on imaging tests, the treatment also didn’t improve people’s brain markers or their overall neurodegeneration.

“Valacyclovir was not efficacious with cognitive worsening for the primary outcome,” the researchers wrote in their paper, published Wednesday in JAMA.

The future of a viral link

As damning as these results are, they don’t completely sink the idea that viruses can contribute to at least some cases of Alzheimer’s.

It often takes time before the damaging brain changes seen in Alzheimer’s become apparent. And by the time someone is experiencing Alzheimer’s symptoms, it might simply be too late to slow the disease’s progression by treating infections that knocked the first domino down, so to speak, many years earlier.

Indeed, this might be true for other drivers of Alzheimer’s. Scientists are now testing, for instance, whether anti-amyloid drugs can prevent or slow the illness in people genetically destined to have Alzheimer’s decades before they should become sick.

While a similar approach isn’t safe to test out with the viral hypothesis, we already have a reliable method for preventing some viral illnesses: vaccines. And several studies lately have found evidence that vaccinating people against shingles, caused by the reactivation of another herpesvirus (the varicella-zoster virus), can lower their risk of later being diagnosed with dementia.

“Might there be a role at the population level for vaccination? Maybe?,” said Knopman, who wrote an editorial accompanying the study in JAMA.

To be clear, more research is needed to confirm a causative link between shingles and Alzheimer’s, as well as the potential protective role of vaccination. But it might represent the hopeful silver lining to this otherwise glum news.