Page last updated at 17:00 GMT, Wednesday, 11 June 2008 18:00 UK

Dual action Alzheimer's drug hope

Alzheimer's cell
Sticky clumps in the brain kill key nerve cells

Experimental drugs are being hailed as a potentially exciting step forward in the treatment of Alzheimer's.

The drugs, still in clinical trials, form a new class called gamma-secretase modulators (GSM).

A study in Nature shows they cut levels of the protein that forms the sticky clumps associated with Alzheimer's.

In addition, the international research team found the drugs boost levels of shorter pieces of the same protein which help to inhibit clump formation.

This is an exciting step forward towards a potential new treatment for Alzheimer's disease
Rebecca Wood
Alzheimer's Research Trust

The clumps - or plaques - are formed of long pieces of amyloid beta protein, and are thought to cause the breakdown of communications between brain cells and lead to the development of dementia.

But shorter pieces of amyloid beta stop the longer pieces from sticking to each other.

The researchers compared the dual action of GSMs with that of drugs which help reduce the risk of heart problems by both lowering levels of harmful cholesterol, and raising levels of cholesterol which has a beneficial effect.

The researchers found that GSMs stick to amyloid beta protein that is already in the brain, preventing it from sticking together.

Amyloid beta is created by an enzyme that chops up a larger protein called APP.

But the latest research found that GSMs do not target APP, but the structure of beta amyloid itself.

The researchers said this was significant, as it showed beta amyloid can be targetted directly by drugs.

Researcher Dr Todd Golde, a neuroscientist at the Mayo Clinic in Jacksonville, said: "This broadens the notion of what drugs can do and therefore has wide-reaching implication for future drug discovery for many different disorders."

Human trials

Doctors are in the third and final phase of trials on human volunteers to test the first GSM, a molecule called tarenflurbil, branded as Flurizan.

Several more drugs in the class are set to enter human trials in the next year or two.

Rebecca Wood, of the Alzheimer's Research Trust, said: "This is an exciting step forward towards a potential new treatment for Alzheimer's disease.

"Scientists may be able to use this proof-of-principle research to develop a new class of drugs that specifically target this mechanism [the build up of plaques] in an effort to slow or prevent the development of Alzheimer's disease.

"Finding a way to prevent or delay the onset of dementia, even for a couple of years, would make a significant difference to the 700,000 people in the UK living with dementia and their families."

Professor Clive Ballard, director of research at the Alzheimer's Society, said the research could lead to "important new opportunities to develop clinically effective drugs".

However, he added: "Clinical trials are extremely expensive and a large increase in investment in dementia research is drastically needed to turn these exciting scientific discoveries into new treatments for people with Alzheimer's disease."


SEE ALSO
Alzheimer's disease
08 Jan 04 |  Medical notes

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