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Alzheimer’s: new drug offers hope for treatment

Alzheimer’s: new drug offers hope for treatment

Alzheimer's drug in final stages of major trial; doctors and scientists are cautiously optimistic

Alzheimer’s: new drug offers hope for treatment

Doctors and researchers are cautiously optimistic that an effective treatment for Alzheimer’s disease could be on the way, after a drug has been shown to successfully target the most visible sign of the disease in the brain.

Findings from a small trial of the drug suggest it effectively switched off production of toxic amyloid proteins that lead to the sticky plaques seen in the brains of Alzheimer’s patients.

The drug is undergoing a major clinical trial, due to be reported next year. If the tablet, produced by pharmaceutical giant Merck, is also shown to slow the pace of mental decline it could be the first treatment for Alzheimer’s to be licensed in more than a decade.

Professor John Hardy, a neuroscientist at UCL (formerly University College London) who proposed amyloid proteins play a central role in Alzheimer’s, welcomed the results.

Matt Kennedy, who led the trial at Merck, said: “Today there are very limited therapeutic options available for people with Alzheimer’s disease, and those that exist provide only short-term improvement to the cognitive and functional symptoms. They do not directly target the underlying disease processes. There is an urgent need for [these].”

The new therapy is designed to do this by halting the steady production of amyloid-beta proteins, which clump together in sticky plaques in the brains of Alzheimer’s patients. It is thought the accumulating proteins kill off healthy neurons, leading to memory loss, cognitive decline and changes to personality.

Kennedy said it was too early to predict when a drug might reach the market if the next step is successful.

In the trial, published in the journal Science Translational Medicine this week, 32 patients with early-stage Alzheimer’s were given the drug – verubecestat – daily for seven days. Healthy volunteers were given the drug for up to two weeks.

This was not long enough to show visible changes to the accumulation of plaques in the brain. However, samples taken from the fluid surrounding the brain showed the drug had reduced the levels of two compounds known to be the building-blocks for abnormal amyloid proteins.

Hardy said the changes to the biomarkers convince him the drug is successfully targeting the build-up of plaques. The uncertainty was whether this would convert into cognitive benefits for patients.

“What we have to be worried about is that the plaques have set off other pathologies – that it is too late,” he said.

The drug works by blocking a brain enzyme called BACE1, which fuels the production of two small molecules that link to form amyloids. Mutations in genes related to BACE1 have been found in people who appear to be protected against Alzheimer’s.

Earlier attempts to develop drugs that inhibit BACE1 have failed due to side-effects such as liver and eye problems.

The Merck drug is understood to have few side-effects and will be the first of its kind to make it into the major trial. The company is running two trials in 1500 patients with mild to moderate Alzheimer’s and another 2000 patients in the earliest stage of the disease. The results of the first of these are due to be reported in July 2017.

Rosa Sancho of Alzheimer’s Research UK said verubecestat is one of several drugs heading into the final stages of clinical testing.

In August the biotech firm Biogen has reported promising results in testing of another drug which targets the plaques. Its drug aims to sweep the proteins away once they appear rather than Merck’s approach of halting production of proteins in the first place.

“With us, it’s a question of switching off the tap. With them it’s mopping up the water,” said Merck spokesman Ian McConnell.

Hardy suggested Merck’s drug is likely to be far cheaper and easier to produce than Biogen’s, which involves injecting patients with antibodies.

THE COST OF ALZHEIMER’S

According to the most recent international study, the number of people with dementia worldwide will nearly double every 20 years. The 2015 World Alzheimer Report projected that global healthcare costs related to dementia will escalate from $US818b last year to $1 trillion in 2018.

In Australia and New Zealand, the total cost of dementia has risen by 40% since 2010 – higher than the global average of 35%.

Alzheimer’s Australia estimates there are more than 353,800 Australians living with dementia. This number is expected to increase to 400,000  in less than five years and almost 900,000 by 2050.

It predicts dementia will become the third greatest source of health and residential aged care spending within two decades.

Alzheimers NZ estimates the number of New Zealanders with dementia will nearly treble to over 150,000 by 2050.

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