Source: Observer
Date: 6 December 2008

Drug offers new Alzheimer's hope

A treatment used against epilepsy can protect
the brain from dementia, scientists discover

Robin McKie, science editor

A drug commonly used to control epilepsy could soon have a new role as a treatment for Alzheimer's disease. Researchers have found that sodium valproate, marketed in Britain as Epilim, stimulates the body's natural defences against the disease.

They found that the drug boosted production of an enzyme which prevents the build-up of proteins in brain cells. These accumulations, or plaques, of protein have been shown by researchers to trigger the onset of Alzheimer's.

Crucially, valproate has already been passed by Britain's stringent drug safety watchdog as an epilepsy drug, and could be brought into widespread use fairly rapidly if research results are confirmed, scientists told The Observer.

'We are still in the early days of our work, but are very excited about the potential of valproate,' said the team leader, Professor Tony Turner, of Leeds University's Institute of Molecular and Cellular Biology.

Alzheimer's disease, the most common form of dementia, is a devastating condition in which victims are stripped of their intellectual powers. There is no cure and patients in later stages have to be cared for by their children or in homes or hospitals. It is caused by the accumulation of a protein called amyloid-beta peptide in brain cells. It is believed that amyloid normally plays a minor role in brain growth; however, its presence - in large amounts - is toxic to the brain.

In young and middle-aged people, amyloid is prevented from building up by the enzyme neprilysin (Nep). However, around the age of 60, the brain's output of Nep declines in many individuals, with devastating results. Amyloid plaques spread and brain cells are killed off, resulting in loss of memory, confusion, mood swings, language breakdown, and general withdrawal as a person's senses decline. Gradually, bodily functions are lost.

Jonathan Miller, former president of the Alzheimer's Disease Society, once said: 'The body remains as a constant reminder of a person who was once loved, and indeed still is. It is a hideous memento of what you have lost.'

Drugs that could counter Alzheimer's are being sought urgently by pharmaceutical companies and most efforts have concentrated on chemicals that could destroy amyloid plaques once established in the brain. But Turner, whose work was funded by the Medical Research Council, took a different approach and directed his efforts to reboosting production of Nep, the brain's own anti-amyloid agent.

'We could have tried introducing, [to see if] healthy genes would start brain cells making Nep again,' he said. 'However, that would have been very complicated.' Instead his team looked at a range of chemicals that they thought might switch on production of Nep in the brain; one of them was valproate, which was highly effective in reboosting production. 'The potential of the drug to clear amyloid from the brains of Alzheimer's patients is obvious,' said Turner.

Scientists have warned that an effective anti-Alzheimer's drug is desperately needed. There are 500,000 people living with the disease in Britain, a figure set to double within a generation as the population gets older and becomes more susceptible to the condition. At this level, Alzheimer's will have a significant impact on the nation's economy. It is already estimated that dementia costs the UK more than £17bn a year. In addition, two-thirds of people with late onset dementia live at home, which means families bear the main stress and the biggest burden of the disease.

'What is really exciting is that valproate is a well-tested and well-tolerated drug that has been given to patients with epilepsy for several decades,' Turner added. 'That means that, if further studies show it is efficacious, we could start giving it to patients in only a few years, and not have to wait for lengthy clinical safety trials to be completed.

'However, I must stress that we still have a fair amount of work to do before that becomes possible.'

Dementia: the facts

1 in 14 people over 65 in the UK have dementia, of which Alzheimer's is the most common type. This figure rises to one in six over 80.

2 per cent of government funding through the Medical Research Council was spent on dementia research in 2003-4.

£11 is spent on research into dementia for each person with the condition in the UK. The figure compares with £105 in America.

4.6 million people around the world will develop dementia this year.

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