A simple daily dose of an existing antiviral drug could slow or even halt the progression of Alzheimer’s disease, new research has claimed.
Scientists say experiments have pinpointed a common virus in the development of the disease. They hope that by combating the virus with an antiviral drug, the deterioration caused by the condition in patients might be reduced or even halted.
The dramatic rise in the number of elderly people has resulted in Alzheimer’s disease becoming the fourth most significant illness leading to death in the UK, claiming nearly 50,000 victims each year.
Overall, dementia costs the UK £26 billion each year, mostly borne by private spending on social care, and by 670,000 unpaid carers.
The virus implicated in Alzheimer’s disease is the one known as herpes simplex virus type 1, HSV1, which is the cause of cold sores. This virus, which infects most humans in infancy, remains in the body in a dormant form (like the chicken pox virus), but awakens periodically after stress or other events, and in some people – those who have a specific form – the type 4 form – of the gene called APOE (APOE4), it then causes cold sores.
In elderly people, it is thought that here too the virus becomes active periodically within the brain, and that the damage it causes there is greater in people with APOE4, and that the damage accumulates, eventually leading to the development of Alzheimer’s disease.
The main abnormal features present in Alzheimer’s disease brain are called plaques and tangles. Plaques are abnormal clusters of protein fragments built up between nerve cells, while dead and dying nerve cells contain tangles, made up of twisted strands of another protein. Obviously, experiments to examine the effects of HSV1 on cells in the brain cannot be carried out on humans.
Instead, cells in culture were used and when infected with HSV1, a large increase in the formation of the main components of plaques and tangles, known as amyloid and tau respectively, was found.
However, when an anti-viral drug was added to the cells, these abnormal products were greatly reduced, suggesting that the drug, if administered to patients, could help to halt disease progression.
The antiviral drug acts by preventing the formation of new viruses; thus, in brain, it would restrict virus numbers and spread, and hence reduce the extent of damage.
Professor Ruth Itzhaki, from the University of Manchester, whose team carried out these studies – which are now supported by work in a number of teams worldwide – said: “We want to set up clinical trials to find if the same drug will stop or slow down Alzheimer’s disease’s progression. Unfortunately, pharmaceutical companies are not interested because the particular antiviral, and other similar ones, are off-patent.”
Ruth and her team first began looking at the role the virus played in Alzheimer’s disease because the main symptoms – memory loss and cognitive impairment – occurred in survivors of herpes simplex encephalitis (HSE), a rare and very serious brain disorder caused by HSV1. Also, the main regions of the brain affected in Alzheimer’s are the same as those affected in herpes encephalitis.
Another major discovery of theirs, linking HSV1 directly to the plaques present in sufferers’ brains, was that in Alzheimer’s disease brains (obtained post mortem), the DNA of HSV1 was found to be located within the plaques, supporting the concept that the virus is a cause of their formation.
The findings suggest that if an anti-viral drug is effective in treating the disease, the drug might save the Treasury £50 billion over the next 15 years, (not counting the benefits to the carers).
Ruth added: “We found that the viral DNA was present not only in Alzheimer’s disease patients but also in a high proportion of normal people. We then thought that a genetic factor, one that Alzheimer’s sufferers have which most normal people don’t have, might affect the extent of damage caused by the virus – and we subsequently linked the virus effect to APOE4.
“A lot of microbes can cause disease in some people yet can be completely harmless in others. One very obvious example is TB, where only ten per cent of people infected with the bacteria actually develop the disease. Similarly, nearly everybody is infected with the cold sore virus but only a quarter of those infected actually get the sores. Clearly, genetic factors can modulate microbial damage.”
“The concept that you can be infected but not affected seems quite alien to a number of scientists, unfortunately. The association of Alzheimer’s with the genetic factor APOE4 and with HSV1 suggests that it’s the action of both together that constitutes a major cause of the disease. The fact that we found APOE4 to be a risk factor for cold sores also, and that the sores are definitely caused by the virus, supports that concept”
Ruth and her team are now trying to secure funding from grant-giving bodies, or pharmaceutical companies, for a clinical trial of an antiviral drug.