There is more hope than ever for medicines that can treat and even prevent Alzheimer’s disease because of the large quantity and diversity of drugs being tested in clinical trials, experts have said.
An annual report has found there are 138 substances being tested globally, which target different aspects of the disease.
The number of drugs entering early-stage trials has risen from 27 last year to 48 this year.
“What strikes me is not just the number of new drugs, which is increasing year on year, but their range of targets, the range in which they work, giving us multiple shots on goal,” said Professor James Rowe, professor of cognitive neurology at the University of Cambridge.
However, families should not expect new treatments imminently, as drugs can take 10 to 15 years to progress from the earliest stage of trials to reach the clinic.
And most of the drugs are in early-stage trials, which often find the medicine fails to work, said Professor Rob Howard, a professor of old age psychiatry at University College London.
“What this paper is showing us is that the pipeline of drug development is growing. It’s diversifying and accelerating,” said Sheona Scales, director of research, Alzheimer’s Research UK.
Some of the drugs are being tested in young people at high risk of Alzheimer’s (Photo: Xavier Lorenzo/Getty Images/iStockphoto)Alzheimer’s, the most common form of dementia, is one of the leading causes of death in western countries such as the UK. But current medicines can only slightly alleviate the symptoms, of memory loss and confusion.
Two new antibody treatments have recently been approved, which were designed to rid the brain of a protein called amyloid, thought for a long time to be the root cause of the disease.
But they have not been used in the NHS, because, while they slightly slowed progression of memory loss in trials, the difference was too small to be noticeable by patients or their families. They also caused dangerous side effects such as strokes and brain swelling.
For decades, the leading theory of Alzheimer’s has been that it is a build-up of amyloid in the brain that causes the death of brain cells and loss of synapses – the connections between brain cells – which leads to memory loss.
But the poor performance of various amyloid-destroying drugs has led scientists to develop medicines that target other aspects of the disease.
Amyloid definitely does build up in Alzheimer’s disease, but so does another protein called tau. Alzheimer’s researchers generally fell into two rival groups, those who favoured targeting one or the other, with the amyloid camp being far bigger.
The new analysis finds that 11 per cent of drugs in Alzheimer’s trials now target tau.
Protecting brain cells
While we still don’t know if amyloid or tau is more important in Alzheimer’s, scientists are sure that the condition involves the death of brain cells and loss of the synapses between them. The loss of brain tissue can be seen when people have brain scans, as the cavities within their brain are enlarged.
Drugs that are designed to protect brain cells and their synapses make up 6 per cent of the total.
Another idea is that proteins build up because of poor functioning of the brain’s immune cells, involving inflammation within the brain. “This contributes to the damage associated with Alzheimer’s disease,” said Dr Emma Mead, chief scientific officer for Oxford Drug Discovery Institute.
“Neuro-inflammation is a highly active area of therapeutic development, with 24 drugs representing 17 per cent of the pipeline and clinical development.”
One of the inflammation-targeting drugs is semaglutide, the weight-loss injection sold as Wegovy (or Ozempic when used for diabetes). While this suppresses appetite, animal research suggests it also reduces chronic inflammation.
It is being tested in people with Alzheimer’s disease in tablet form.
Existing medicines
A common strategy in medical research is to retest medicines already in use for other conditions, and this makes up 33 per cent of the drugs in development. They include an antidepressant and metformin, which is used for type 2 diabetes.
Many drugs have several effects on the body. “A blood pressure tablet may have a side effect that it can help accelerate the clearance of junk proteins like amyloid and tau,” said Professor Rowe. “That’s a very powerful way potentially to accelerate access to safe and effective treatments.”
Cognitive enhancers
The two existing medicines for Alzheimer’s that help alleviate symptoms do not tackle the biological cause, but seem to help brain cells work more effectively. Several other drugs are being tested for this effect, making up 14 per cent of the research pipeline.
There are other drugs in development that are aimed to ease the behavioural symptoms of Alzheimer’s, such as agitation and aggression.
Just because treatments are aimed at easing symptoms rather than changing the biology doesn’t mean they can’t be very helpful , said Professor Howard. “We don’t have any treatment to slow down Parkinson’s disease but we have symptomatic treatments, that boost dopamine, and they make a massive difference,” he said.
“I anticipate if we’re going to see any advances in the treatment of Alzheimer’s disease in the next five to 10 years, it will be through better symptomatic treatments, not through better disease modifiers.”
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