Using Valacyclovir to Treat Early Symptomatic Alzheimer’s Disease
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on January 16th, 2026
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During the latent stage after initial site infection with herpes simplex virus HSV-1 and HSV-2, the virus can infiltrate trigeminal ganglion and migrate to the brain via retrograde axonal transport. In animal study, HSV can infect neuronal and glial cells causing accumulation of amyloid β-protein, and tau protein phosphorylation, a hallmark of Alzheimer’s disease. Moreover, a postmortem study found that 90% of patients with Alzheimer’s disease had detectable HSV-1 DNA in the amyloid plaques. With funding from the United States National Institutes on Aging, a study was commissioned to examine the effectiveness of valacyclovir in treating symptomatic Alzheimer’s disease.
The phase 2 clinical trial included 120 participants with an average age of 71 years old who had been diagnosed with Alzheimer’s disease or mild cognitive impairment. Using the 11-Item Alzheimer’s Disease Assessment Scale Cognitive Subscale to evaluate the patient’s memory and language utilization skill yields an average score of around 20, with 70 indicating the most debilitating cognitive impairment. Further assessment was also performed with other tests to evaluate memory, attention, executive functions, visuospatial skills, and ability to perform daily life activities. Serum analyses found that 80% of the participants had antibodies against HSV-1, and more than 30% were immune against HSV-2.
The patients were randomly assigned to be treated orally with either placebo or valacyclovir at an initial daily dose of 2 grams, which is gradually to 3 grams by the second week and to 4 grams by the fourth week. Valacyclovir is an antiviral that specifically targets viruses in the herpesvirus family. The medication is metabolized into Aciclo-GTP that can interrupt viral replication by inhibiting the viral DNA polymerase.
After 78 weeks, the researchers found that participants treated with valacyclovir had more reduction in their 11-item ADAS-Cognitive Subscale score than their counterparts treated with placebo. However, comparison using the other cognitive assessment scale did not yield significant differences between the two groups. Besides the lack of effectiveness, the researchers recommended that valacyclovir should not be used, as patients treated valacyclovir reported a higher frequency of elevated serum creatine level and gastrointestinal adverse events such as diarrhea, nausea, and abdominal pain. The researchers also noted that the neurotoxicity associated with valacyclovir could have interfered with the cognitive assessment findings. Nonetheless, brain imaging of patients treated with valacyclovir did not result in any significant reduction of amyloid plaque, and tau protein.
The phase 2 clinical trial included 120 participants with an average age of 71 years old who had been diagnosed with Alzheimer’s disease or mild cognitive impairment. Using the 11-Item Alzheimer’s Disease Assessment Scale Cognitive Subscale to evaluate the patient’s memory and language utilization skill yields an average score of around 20, with 70 indicating the most debilitating cognitive impairment. Further assessment was also performed with other tests to evaluate memory, attention, executive functions, visuospatial skills, and ability to perform daily life activities. Serum analyses found that 80% of the participants had antibodies against HSV-1, and more than 30% were immune against HSV-2.
The patients were randomly assigned to be treated orally with either placebo or valacyclovir at an initial daily dose of 2 grams, which is gradually to 3 grams by the second week and to 4 grams by the fourth week. Valacyclovir is an antiviral that specifically targets viruses in the herpesvirus family. The medication is metabolized into Aciclo-GTP that can interrupt viral replication by inhibiting the viral DNA polymerase.
After 78 weeks, the researchers found that participants treated with valacyclovir had more reduction in their 11-item ADAS-Cognitive Subscale score than their counterparts treated with placebo. However, comparison using the other cognitive assessment scale did not yield significant differences between the two groups. Besides the lack of effectiveness, the researchers recommended that valacyclovir should not be used, as patients treated valacyclovir reported a higher frequency of elevated serum creatine level and gastrointestinal adverse events such as diarrhea, nausea, and abdominal pain. The researchers also noted that the neurotoxicity associated with valacyclovir could have interfered with the cognitive assessment findings. Nonetheless, brain imaging of patients treated with valacyclovir did not result in any significant reduction of amyloid plaque, and tau protein.