Killer tangles: microscope image of tau protein aggregating inside a brain cell

Given the field's Cinderella status, the announcement by Aberdeen University researchers in July of a major breakthrough in the treatment of the disease is especially significant. Addressing the International Conference on Alzheimer's Disease (ICAD 2008) in Chicago, the researchers described the astonishing results of clinical trials of a new treatment, that appears to slow the progress of the disorder by 81% over a year. The product – rember^TM – is the first drug to act on the tangles discovered by Alois Alzheimer over a century ago.

The research was led by Professor Claude Wischik, working with TauRx Therapeutics, a Singapore-based company spun out of Aberdeen University. Wischik's team have developed a treatment based on an entirely new approach which targets the tangles, aggregates of abnormal fibres of tau protein forming inside nerve cells in the brain. These aggregates first destroy nerve cells critical for memory and then destroy neurons in other parts of the brain as the disease progresses.

Alzheimer's disease is a degenerative and terminal brain disorder which affects millions of people around the world, and is a major and growing burden on health services in all countries with an ageing population. During the course of its progress there is a build-up in the brain of lesions known as plaques and tangles.

The results of the Phase 2 study of TauRx's treatment strongly suggest that it is possible to halt progression in mild and moderate Alzheimer's. The Aberdeen team is continuing to refine its treatment and hopes that restoration may be possible, at least at the earlier stages, with improved versions of the drug. The ultimate goal is to develop a product that could be widely used at the very earliest stages of the disease, long before patients experience the first symptoms of Alzheimer's.

Professor Wischik and his team have spent 24 years investigating the structure and role of the tangles in the development of the disease. Their key discovery was that the tangles are made up of the tau protein, and that its aggregation or clumping is highly correlated with the progression of Alzheimer's. The researchers found that plaque development, which has been the main focus of research to date, is more a feature of normal ageing and is poorly correlated with dementia.

The team then looked for a drug with the ability to dissolve the tau protein fibres of the tangle and developed rember^TM – a novel form of a chemical with a long history of use in the treatment of other conditions. TauRx, established in Singapore in 2002, has patented the medical use of rember^TM for the treatment and prevention of Alzheimer's. In addition to the Alzheimer’s trials, TauRx is planning a trial in Parkinson’s – in which rember^TM is also expected to prove effective.

"With the world population ageing globally and the enormous burden on health services and economies worldwide, we urgently need to confirm our findings in a larger trial with a view to making this treatment available as soon as possible,” commented Wischik. "World Health Organisation figures indicate that there will be more than one billion people aged 65 and over by 2050, of whom we calculate about half will have tau tangles in their brains. This makes it particularly important to develop new treatments to halt and prevent tangles forming in the brain."

Following the results from the Phase 2 clinical trials, TauRx is now planning a Phase 3 trial which should begin next year. If the Phase 3 trial confirms the Phase 2 findings, the drug could be available by 2012.

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