“Our results suggest that HSV1, together with the host genetic factor, is a major risk for AD, and that antiviral agents might be used for treating patients to slow disease progression.”
Researchers at the University of Manchester have shown that the herpes simplex virus type 1 (HSV1) – the type linked to ‘cold sores’ or ‘fever blisters’ – is a risk factor for Alzheimer’s when it is present in the brains of people who have a specific genetic risk of the disease.(1)
They’ve established that HSV1 causes accumulation of two key proteins believed to be involved in Alzheimer’s development – beta-amyloid (ABeta), the main component of plaques, and abnormally phosphorylated tau (P-tau), the main component of tangles.
“We have found that the viral DNA in AD brains is very specifically located within amyloid plaques,” says Professor Ruth Itzhaki, who led the team in the University’s Faculty of Life Sciences. “This, together with the production of amyloid that the virus induces, suggests that HSV1 is a cause of toxic amyloid products and of plaques. Our results suggest that HSV1, together with the host genetic factor, is a major risk for AD, and that antiviral agents might be used for treating patients to slow disease progression.”
Currently available antiviral agents act by targeting replication of HSV1 DNA, and so the researchers considered that they might be successful in treating AD only if the accumulation of beta-amyloid and P-tau accumulation caused by the virus occurs at or after the stage at which viral DNA replication occurs. “If these proteins are produced independently of HSV1 replication, antivirals might not be effective,” says Professor Itzhaki.
“We investigated this and found that treatment of HSV1-infected cells with acyclovir, the most commonly used antiviral agent, and also with two other antivirals, did indeed decrease the accumulation of beta-amyloid and P-tau, as well as decreasing HSV1 replication as we would expect.”
[See their full text report, published Oct 17 by PloS One – “Antivirals Reduce the Formation of Key Alzheimer’s Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1.”]
“This is the first study investigating antiviral effects on AD-like changes and we conclude that since antiviral agents reduce greatly beta-amyloid and P-tau levels in HSV1-infected cells, they would be suitable for treating Alzheimer’s disease,” Dr. Itzhaki continues.
Advantages of an Effective Antiviral Therapy
“The great advantage over current AD therapies is that acyclovir would target only the virus, not the host cell or normal uninfected cells. Further, these agents are very safe and are relatively inexpensive. Also, by targeting a cause of Alzheimer’s disease, other viral damage, besides beta-amyloid and P-tau, which might be involved in the disease’s pathogenesis, would also be inhibited.
Next Steps in Research
According to Dr. Itzhaki:
• “The next stage of our research – subject to funding – will focus on finding the most suitable antiviral agent – or combination of two agents that operate via different mechanisms – for use as treatment.
• “We then need to investigate the way in which the virus and the genetic risk factor interact to cause the disease, as that might lead to further novel treatments.
• “Eventually, we hope to begin clinical trials in humans but this is still some way off yet and again will require new funding.”
1. Appears to refer to people carrying the e4 version of the APOE or “lipoprotein-making” gene. The e4 allele increases an individual’s risk for developing memory symptoms, Alzheimer’s and other disorders such as cardiovascular disease (see http://ghr.nlm.nih.gov/gene/APOE). People who inherit one copy of this allele have an increased risk, and inheriting two copies further boosts the risk.
Source: University of Manchester news release, Oct 17, 2011