The virus that causes cold sores may be one of the main causes of Alzheimer’s disease, according to research that suggests that existing drugs could be used to treat the most common form of dementia.

Compelling new evidence found by British scientists has implicated the cold sore virus, known as herpes simplex virus 1 (HSV1), in up to 60 per cent of Alzheimer’s cases.

Though the findings from the University of Manchester remain preliminary, they could transform scientific understanding of a brain disorder that affects more than 400,000 people in Britain, and open an entirely new approach to treating it.

The insight is particularly encouraging because cheap antiviral drugs that can control HSV1 infections, such as acyclovir or Zovirax, have been available for many years, and are sufficiently safe to be sold over the counter.

If HSV1’s role is confirmed, and antivirals are proved effective against the virus in the brain, the research would raise the prospect of stopping the progressive damage caused by Alzheimer’s in its tracks. This would allow hundreds of elderly people to avoid progressive cognitive decline that is highly distressing to them and their families, and to lead independent lives.

“One thing that is exciting about our research is that we already have drugs that have been used for a relatively long time against HSV1, which are cheap and well tolerated,” said Professor Ruth Itzhaki, who leads the research group. “If we are right, there is a good chance we could make progress quite quickly.”

Despite this potential, the Manchester team is struggling to obtain funding for the next stage of its research. Grant applications to test the HSV1 hypothesis in animal models have been turned down.

Professor Itzhaki said that if she could raise money to start animal studies, these should give preliminary indications of whether HSV1 was genuinely involved in Alzheimer’s within a year or so. The next step would be to test antivirals in early-stage Alzheimer’s patients in a clinical trial, which would take three to five years.

Although HSV1 is very common, infecting most adults and causing cold sores in about 20 to 40 per cent of them, the research does not suggest that everybody or even most people who suffer from cold sores will get Alzheimer’s. If the link is proved, it would be one of several factors, some of which are genetic, and early indications are that HSV1 might contribute to up to 60 per cent of cases.

HSV1’s potential role in Alzheimer’s is in the formation of plaques of beta amyloid protein that build up in the brain cells, which are thought to be its main cause.

Professor Itzhaki’s group has been investigating this process for several years, and last year published research showing that HSV1 can promote the formation of beta amyloid plaques in cell cultures grown in the laboratory.

The new research, published in the Journal of Pathology, goes significantly farther, as it has found firm evidence of HSV1 infection in protein plaques in the brain cells of Alzheimer’s patients.

The scientists used a sophisticated genetic analysis technique called the in-situ polymerase chain reaction to detect HSV1 DNA in these protein plaques. This shows that the virus is associated with such build-ups, and suggests that it might be a significant cause.

HSV1, a cousin of the HSV2 virus that causes genital herpes, hides in the peripheral nervous system in a latent form, and periodically becomes active to cause cold sores in 20 to 40 per cent of carriers. The Manchester scientists believe that HSV1 may enter the brain and become active as people’s ageing immune systems lose the ability to keep it contained. It may then promote the build-up of beta amyloid and thus the onset of Alzheimer’s.

Professor Itzhaki said: “We suggest that HSV1 enters the brain in the elderly as their immune systems decline and then establishes a dormant infection from which it is repeatedly activated by events such as stress, immuno-suppression and various infections.”

Antiviral drugs such as acyclovir, sold under the brand name Zovirax, can control HSV1 during the active phase of its life cycle, during which it causes cold sores.

A critical task for the next stages of research will be to determine whether HSV1 contributes to plaque formation while in its latent or active phase. If active HSV1 is responsible, it should respond to treatment: antivirals are known to be effective in the brain, as they are used to treat a rare and dangerous complication of herpes infections: herpes simplex encephalitis.

Matthew Wozniak, a member of the Manchester team, said that antiviral treatment would have big advantages over other approaches to Alzheimer’s therapy. “Antiviral agents would inhibit the harmful consequences of HSV1 action, in other words, inhibit a likely major cause of the disease irrespective of the damaging processes involved, whereas current treatments at best merely inhibit some of the symptoms.”

Memory loss

- First described by German psychiatrist Alois Alzheimer in 1906, the disease is degenerative, incurable and the most common form of dementia

- It is most prevalent in the over-65s, though early onset Alzheimer’s can occur much younger

- The first symptom is often short-term memory loss and can develop into mood swings, confusion, irritability, loss of longer term memory and language breakdown

- More than 700,000 people suffer from the disease in the UK

- 60,000 deaths a year are directly related to dementia. Delaying its onset by five years would halve the number of related deaths

Sources: Alzheimer’s Society, Times Archive

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