Alzheimer’s breakthrough

Scientists home in on molecule which halts development of disease

Cambridge scientists raise prospect of new generation of treatments after finding technique to limit development of biggest cause of dementia.

Scientists have found a method which could potentially stop the growth of Alzheimer’s disease in its tracks, raising the prospect of a wave of new treatments for the condition.

A team at Cambridge University, working with partners in Sweden and Estonia, has identified a molecule which can block the progress of Alzheimer’s at a crucial stage in its development.

Not only is it the first time that experts have identified a means of breaking the cycle leading to the development of Alzheimer’s but they believe the technique could be used to identify other molecules as future treatments to curb the growth of the condition.

Charities hailed it as an “exciting” discovery.

More than 520,000 people in the UK are estimated to be living with Alzheimer’s, by far the most common cause of dementia.

Dementia-related conditions are already the biggest cause of death among women in Britain and only narrowly outranked by heart disease and cancer for men.

Alzheimer’s develops when proteins in the brain malfunction and then stick together into fibres. They in turn eventually form clusters called oligomers which are toxic to nerve cells.

The second stage of that process is believed to set off a chain reaction which multiplies the number of clusters, hastening the development of the most devastating effects.

Experts at the Centre for Misfolding Diseases in Cambridge’s Chemistry Department have identified that natural proteins called Brichos, can stick to the fibres preventing them merging with others and forming the damaging clusters, therefore limiting the effects.

They believe the method used could help them identify other so-called “chaperone molecules” which could attach themselves in a similar way raising the prospect of a new generation of treatments.

Dr Samuel Cohen, a research fellow at St John’s College, Cambridge, and a lead author of a paper in the journal Nature Structural & Molecular Biology, said: “A great deal of work in this field has gone into understanding which microscopic processes are important in the development of Alzheimer’s disease.

“Now we are now starting to reap the rewards of this hard work. Our study shows, for the first time, one of these critical processes being specifically inhibited, and reveals that by doing so we can prevent the toxic effects of protein aggregation that are associated with this terrible condition.”

He explained that the breakthrough came after the researchers worked out how to model what might happen if one stage in the process of developing Alzheimer’s was effectively “switched off” and then experimented with different molecules to do this. They then confirmed their findings through tests involving mice.

“It may not actually be too difficult to find other molecules that do this, it’s just that it hasn’t been clear what to look for until recently,” he added.

“It’s striking that nature – through molecular chaperones – has evolved a similar approach to our own by focusing on very specifically inhibiting the key steps leading to Alzheimer’s.

“A good tactic now is to search for other molecules that have this same highly targeted effect and to see if these can be used as the starting point for developing a future therapy.”

Dr Ian Le Guillou, research officer at Alzheimer’s Society, said: “This study reveals a new way in which our brain’s natural defences guard against the build-up of amyloid protein which clumps together in Alzheimer’s disease.

“While most current research attempts to break up these clumps or reduce their impact on brain cells, this new discovery identifies a molecule that reduces the rapid accumulation of the toxic clumps.

“This revelation is exciting as it gives scientists a whole new way of looking at the problem, opening the doors to possible new treatments.”

Dr Laura Phipps of Alzheimer’s Research UK, said: “This detailed study has revealed a potential way to prevent the build-up of amyloid, and highlights a possible new avenue for research into new treatments for Alzheimer’s disease.

“Researchers are working hard to identify the molecular process that are most toxic to nerve cells in Alzheimer’s and this technically challenging study has revealed clues to how to block one important chain of events in the disease.

“Alzheimer’s is a complex disease, and further research will be needed to understand whether this approach could help stop its catastrophic effects in people.

“The more we know about the different molecular mechanisms driving Alzheimer’s, the better equipped we will be to fight the disease. Investment in research is critical if laboratory findings like these are to translate into benefits for patients, and Alzheimer’s Research UK’s Drug Discovery Alliance is well-placed to help realise this ambition.”