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Wednesday, 15 May, 2002, 18:07 GMT 19:07 UK
Dementia drug potential hailed
Injection
The new drug may tackle Alzheimer's disease
A drug aimed at helping people with a rare illness could hold promise for patients with Alzheimer's disease, says a UK scientist.

An international team including scientists from London and Southampton believes the discovery has a chance of providing an effective treatment for this incurable brain disease.

A number of diseases - including Alzheimer's - are characterised by the formation of "plaques", fibrous deposits of protein called amyloid around cells in the affected organ.

Even though these amyloid plaques are unnatural, the body seems unable to dispose of them, and they progressively affect more and more tissue.

It is strongly suspected that in Alzheimer's, the plaques may kill brain cells, playing a key role in the progression of dementia.

Breakthrough

A team from the Royal Free Hospital in North London, led by Professor Mark Pepys, thinks the reason the body cannot break down the plaques is because another body protein, called SAP, coats the amyloid and disguises it from the immune system.

If this SAP could be removed, researchers suggested, perhaps the body could start to remove the amyloid, perhaps halting or even reversing the disease.

Now they have found a drug which removes SAP from the body.

It is designed to latch on to more than one SAP molecule, and then be recognised and extracted from the blood by the liver.

In mouse experiments, not only does it radically reduce the amount of SAP circulating in the bloodstream, but also appears to lead to a reduction in the overall amount of amyloid.

Safe in humans

In addition, the drug showed no signs of being toxic to mice, and doctors were able to move straight to tests on a small number of human patients.


We don't have to get the drug into the brain, which is a great advantage

Professor Mark Pepys, Royal Free Hospital, London
These people all had an illness called systemic amyloidosis - in which plaques form and gradually disrupt various organs in the body, including, in some cases, the heart and kidneys.

These plaques eventually cause the organ to fail, with devastating consequences to the patient. Again, no significant side effects appeared, and blood levels of SAP fell.

More importantly, the condition of most of the patients did not worsen while they were on the drug.

Brain access

Professor Pepys told BBC News Online that these preliminary results were "encouraging" - but would have to be repeated on many more patients.


There are a number of hurdles to jump before we will see whether this drug might help people with Alzheimer's disease

Dr Richard Harvey, Alzheimer's UK
A problem with any drug aimed at the brain is how to bypass the "blood-brain barrier", a filter designed to stop large, potentially harmful, molecules from coming into contact with delicate brain tissue.

The new drug molecule is large - but Professor Pepys said that this might not prove a problem.

It was so successful in reducing the level of SAP in the blood, he said, that SAP from the amyloid plaques began to make its way back into the bloodstream, where it was transported away from the brain.

He said: "By reducing the amount of SAP in the blood, we can also reduce the level in amyloid plaques in the brain.

"It means we don't have to get the drug into the brain, which is a great advantage."

'More evidence needed'

Dr Richard Harvey, of charity Alzheimer's UK, welcomed the advance, but urged caution.

He said: "There are a number of hurdles to jump before we will see whether this drug might help people with Alzheimer's disease.

"It is widely hypothesized that the amyloid plaques are the triggering processes in Alzheimer's disease, and these somehow lead to tangle formation. This is far from being proved.

"Until there is much wider safety testing it will be difficult to assess how safe the drug is.

"As with the recently discontinued Alzheimer vaccine, major safety issues may not appear until the drug has been tested on hundreds or even thousands of patients."

Diabetes help

It has also been suggested that the drug, or one similar to it, might be able to help people with type II, or adult-onset, diabetes.

This is because amyloid plaques have also been noticed around crucial insulin-producing cells in the pancreas in patients with the disease.

However, Dr Ann Clarke, from the Islet Amyloid Laboratory at the Oxford Radcliffe Infirmary, said that she was not convinced reducing amyloid could offer improvements for patients.

She said: "The thing about type II diabetes is that you can have it, while having hardly any amyloid, so this drug is not going to cure it."

See also:

20 Dec 00 | A-B
Alzheimer's disease
24 May 01 | Health
Brain diseases discovery
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