Researchers Tested Herpes Drugs for Alzheimer’s. It Backfired

The search for an effective Alzheimer's disease treatment has suffered another setback. This time, medications designed to combat herpes infections have proven unsuccessful.

Columbia University researchers recently released the disappointing results of their clinical trial. The study found that antiviral treatment did not improve cognition in individuals with both diagnosed herpes and early-stage Alzheimer's. In fact, the group receiving the antiviral medication experienced a greater decline in cognitive function compared to those receiving a placebo. Experts not involved in the study suggest that while these findings don't completely dismiss a potential connection between viral infections and Alzheimer's, the use of these drugs to treat dementia is not advisable.

Dr. David Knopman, a Mayo Clinic neurologist, emphasized that antiviral therapy has no role in treating individuals experiencing cognitive impairment. He is not affiliated with the research.

The Viral Hypothesis of Alzheimer's

Alzheimer's disease, the most prevalent form of dementia, currently affects over 7 million people in the United States.

The disease is characterized by elevated levels of misfolded amyloid beta and tau proteins in the brain. That said, the reality is a bit more complicated. the precise roles of these proteins in driving the disease, and the initial triggers of the destructive processes that ultimately affect the brain, remain unclear.

Recent research has explored the possibility that certain viruses and other pathogens may contribute to or even cause Alzheimer's disease. This is known as the viral hypothesis. Some studies have indicated that herpesvirus infections can stimulate the accumulation of amyloid beta plaques in mice with human-like brain cells. Furthermore, individuals who died from Alzheimer's were found to have a higher prevalence of herpesviruses in their brains compared to those without the condition.

To date, the evidence supporting a viral connection remains indirect. That said, the reality is a bit more complicated. if viruses are indeed a cause, then antiviral treatments could potentially prevent or slow the disease's progression by addressing the underlying infection. This is the premise the researchers aimed to investigate.

Trial Shows No Benefit, Cognitive Worsening

The controlled trial involved 120 participants, all diagnosed with either probable Alzheimer's disease or mild cognitive impairment likely to progress to Alzheimer's. All participants also tested positive for antibodies to herpes simplex virus type 1 or 2 (HSV-1 or HSV-2). HSV-1 is commonly associated with cold sores, while HSV-2 typically causes genital herpes, though either type can cause infections in other areas.

For 18 months, participants were randomly assigned to receive either a daily placebo or valacyclovir (Valtrex), a standard medication for managing HSV and other herpesvirus infections.

The study concluded that the group treated with valacyclovir experienced a significantly greater progression of cognitive decline compared to the placebo group. Imaging tests also revealed that the treatment failed to improve brain markers or reduce overall neurodegeneration.

The researchers stated in their JAMA-published paper that valacyclovir was not effective and was associated with cognitive worsening for the primary outcome.

Implications for Future Research

Despite these discouraging results, the idea that viruses may play a role in some Alzheimer's cases is not entirely disproven.

The brain changes associated with Alzheimer's can take years to become evident. By the time symptoms appear, it may be too late to slow the disease's progression by targeting infections that may have initiated the process years earlier.

This may also be true for other potential drivers of Alzheimer's. For example, scientists are currently investigating whether anti-amyloid drugs can prevent or slow the disease in individuals genetically predisposed to developing Alzheimer's decades before symptoms are expected to emerge.

While proactively testing the viral hypothesis in a similar way is not currently feasible, effective vaccines already exist for preventing some viral illnesses. Recent studies have suggested that shingles vaccinations, which target the varicella-zoster virus (another herpesvirus), may reduce the risk of later dementia diagnoses.

Dr. Knopman, who also authored an editorial accompanying the study, suggested that vaccination might play a role at the population level. That said, the reality is a bit more complicated. he also clarified that further research is necessary to confirm a causal relationship between shingles and Alzheimer's, as well as the potential protective effects of vaccination. This potential link offers a glimmer of hope amidst otherwise disheartening news.