Sun, Nov 10th, 2013

Alzheimer’s cure is close: Experts hail new drug breakthrough

A CURE for Alzheimer’s is moving closer with trials of breakthrough drugs that could halt the crippling effects of the disease.

A research team in Switzerland has discovered how potent new compounds work in the body to fight the brain condition without causing harmful side-effects.

The major development, which offers hope to millions of sufferers, was described as “tremendously encouraging” yesterday.

It makes it possible to tailor treatments so they target the toxic plaques that clump together in the brain and cause confusion and memory loss.

This has been achieved by working out how an enzyme triggers the destruction of neurons in the brain. Dirk Beher, co-author of a report on the research, said: “We have obtained extraordinary knowledge about how the enzyme gamma secretase can be modulated. This knowledge will be invaluable for developing even better targeted drugs to fight the disease.”

Clinical trials of two new classes of drug had to be abandoned in 2010 because the compound being tested completely blocked the function of gamma secretase, resulting in serious side-effects, such as internal bleeding and skin cancer.

Senior author Dr Patrick Fraering said: “Scientists have been trying to target gamma secretase to treat Alzheimer’s for over a decade.

“Our work suggests that next-generation molecules, by modulating rather than inhibiting the enzyme, could have few, if any, side-effects. It is tremendously encouraging.”

Alzheimer’s is characterised by a build-up of toxic amyloid plaques which clump together in the brain and destroy surrounding cells. A protein called APP triggers this process after it is cut by the enzyme gamma secretase and released outside the cell where it forms amyloid.

For reasons not yet fully understood, APP can be cut in several different places, producing amyloid pieces of varying lengths. Halted

Only the longer forms carry the risk of clumping into plaques. People with Alzheimer’s produce an abnormally high number of these longer forms.

The two new drugs being tested target the enzyme that cuts APP.

Until now, little has been understood about the mechanism involved. But this latest research by scientists at the Ecole Polytechnique Federale de Lausanne, which is published in the journal Nature Communications, has been able to shed more light on the process.

Researchers found that the drugs change the location where the enzyme cuts APP, producing shorter versions which cannot clump together into the dangerous plaques.

Dr Simon Ridley, head of research at Alzheimer’s Research UK, said: “After trials of a previous treatment designed to block gamma secretase had to be halted, it is positive to see this class of drug being refined in order to minimise side-effects. This study shows the latest gener ation of these drugs may target gamma secretase in a much more selective way, potentially reducing such harmful effects.

“We would still need to see clinical trials of these drugs completed before we will know whether they can benefit people with Alzheimer’s disease.”

source: www.express.co.uk

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