Cancer drug could halt build-up of toxic Alzheimer’s protein

Science Advances: An anti-cancer drug suppresses the primary nucleation reaction that produces the toxic Aβ42 aggregates linked with Alzheimer’s disease

Researchers at the University of Cambridge have identified a cancer drug that could halt the build-up of amyloid – a toxic hallmark protein in Alzheimer’s disease. The research was carried out in nerve cells and worms in the laboratory, and published in the journal Science Advances on 12 February 2016.

The team carried out a screen in the laboratory to find experimental drugs that can stick to the amyloid protein. A screen is a large experiment where researchers test thousands of different chemical compounds to see whether they interact with a target protein. The team identified a drug called bexarotene – currently used to treat a type of skin cancer.

The researchers carried out detailed chemical experiments to look at the impact of bexarotene on amyloid clumps. In experiments in test tubes, they found that bexarotene interferes with early and critical steps in the formation of these toxic clumps.

They then went on to investigate whether bexarotene could stop the formation of toxic amyloid clumps in a species of worm called C.elegans. The researchers used genetically modified C.elegans, which produce amyloid in the muscles of their body walls, leading to problems with movement. They found that bexarotene could slow the build-up of amyloid clumps in their muscles and delay movement difficulties.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“We know that the accumulation of amyloid is a hallmark feature of Alzheimer’s and that drugs to halt this build-up could help protect nerve cells from damage and death. A recent clinical trial of bexarotene in people with Alzheimer’s was not successful, but this new work in worms suggests the drug may need to be given very early in the disease. We will now need to see whether this new preventative approach could halt the earliest biological events in Alzheimer’s and keep damage at bay in further animal and human studies.

“Bexarotene hit the headlines in 2012 after a study in mice suggested the drug could clear amyloid from the brain, but further studies to reproduce this finding have been mixed. This early research in worms suggests that bexarotene could act earlier in the process to interfere with amyloid build-up, but it is too soon to conclude that the drug could be used as a way to prevent Alzheimer’s and whether this would be a safe approach in healthy people. Bexarotene is the subject of a lot of scientific interest as researchers seek to understand why studies have yielded differing results and it’s important that scientists fully examine how this drug works to inform any future clinical trials in Alzheimer’s.

“Alzheimer’s Research UK is committed to finding effective treatments for the 850,000 people in the country living with dementia. Our £30 million Drug Discovery Alliance will take the most promising ideas and accelerate the hunt for new medicines in the clinic. We know that increased investment in dementia research is the only way to tackle this huge medical challenge.”

Source: Alzheimer s Research UK

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