Hope of a cure for Alzheimer’s has been raised after scientists have discovered why decades worth of studies have failed to find a solution.
Attempts to stop the memory-robbing disorder in its tracks have targeted the toxic build-up of amyloid beta in the brains of patients.
This accumulation in the brain gradually destroy neurons and causes memory loss and confusion.
However, researchers at King’s College London now claim that once these clumps have formed it is ‘too late for drugs’ to work.
Instead, they have found targeting a little-known protein that causes the clumps to develop ‘dramatically’ improves signs of Alzheimer’s in mice.
Drug treatments that act on blocking this protein are already available in China and Japan for stroke.
Scientists have raised hopes of an Alzheimer’s cure after discovering why decades worth of studies have failed to find ease the condition. They claim unsuccessful medications often target protein clumps in the brain when it is ‘too late’ to stop the disease (stock)
Alzheimer’s – the most common form of dementia – affects around 5.5 million people in the US and 500,000 in the UK, figures show.
The researchers, led by Dr Christina Elliott, discovered that the disease’s progression works like a circuit.
When the protein amyloid-beta starts to clump together in a patient’s brain, it begins to break down nerve cells.
This causes these cells to produce more amyloid-beta, driving their own destruction.
Senior author Dr Richard Killick said: ‘We show that a vicious positive feedback loop exists in which beta-amyloid drives its own production.
‘We think once this feedback loop gets out of control it is too late for drugs which target beta-amyloid to be effective.’
He added: ‘This could explain why so many Alzheimer’s drug trials have failed.’
Rather than focusing on amyloid-beta itself, the researchers believe drug developers should target the protein Dkk1, which stimulates amyloid-beta’s production.
The scientists studied mice with large amounts of beta-amyloid in their brains to test their theory.
When the rodents were treated with the Dkk1-blocking drug fasudil for two weeks, their beta-amyloid levels reduced dramatically.
The results were published in the journal Translational Psychiatry.
Dr Killick said: ‘We have convincingly shown fasudil can protect synapses and memory in animal models of Alzheimer’s, and at the same time reduces the amount of beta-amyloid in the brain.’
The scientists plan to investigate if fasudil could boost brain health and prevent cognitive decline in people with early-stage Alzheimer’s.
Study co-author Professor Dag Aarsland added: ‘As well as being a safe drug, fasudil appears to enter the brain in sufficient quantity to potentially be an effective treatment against beta-amyloid.
‘We now need to move this forward to a clinical trial in people with early stage Alzheimer’s disease as soon as possible.’
Although experts agree the results of the study are promising, some question how blocking Dkk1 could ease Alzheimer’s symptoms.
Professor Tara Spires-Jones, from the University of Edinburgh, welcomed the findings. She said: ‘This paper is scientifically interesting.
‘But there is a long way to go to know whether these results will lead to therapies that will help people with dementia.’
In addition, fasudil’s effects were only tested in the lab and in mice. It is therefore unclear whether the drug will benefit Alzheimer’s patients.
Dr Carol Routledge, from Alzheimer’s Research UK, said: ‘Fasudil is an approved drug for other health conditions.
‘But [it] is currently used in a critical care setting and would need to go through robust safety tests in trials of people with Alzheimer’s disease.’