As far as holy grails in medicine are concerned, you don’t get one much more significant than a cure for dementia. It’s the condition many of us fear most, as the disease slowly but inexorably obliterates the mind.
We’ve been waiting for a breakthrough treatment for decades, yet despite billions spent on drug development and research by governments and companies worldwide, the majority of candidates have fallen by the wayside.
Some experimental medicines have even had the opposite of the intended effect, actually worsening brain function. And the only drugs currently available simply tackle specific symptoms of mild to moderate dementia — there is nothing that can slow down the disease or prevent it.
So, understandably, there was huge excitement and hopeful headlines recently after the first new medicine for Alzheimer’s (the most common type of dementia) in two decades was approved by the U.S. regulator, the Food and Drug Administration (FDA).
As far as holy grails in medicine are concerned, you don’t get one much more significant than a cure for dementia
The drug, aducanumab (brand name, Aduhelm), works by clearing the brain of plaque, formed of a build-up of a sticky protein called amyloid-beta — this has been linked to dying nerve cells and is considered a hallmark feature of Alzheimer’s.
But the approval was controversial because despite clearing the plaque, the drug did not significantly improve patients’ symptoms.
‘The problem is there is absolutely no evidence that reducing amyloid-beta also slows down the course of Alzheimer’s,’ says Robert Howard, a professor of old-age psychiatry at University College London.
‘It’s a bit like removing smoke but not putting the fire out. And it is not a benign treatment; the rate of serious side-effects is quite high.’
Indeed, as many as 40 per cent of those who took the highest dose in trials experienced brain side-effects, which included brain swelling, reported the journal JAMA Neurology this month. And 11 people died during the trials. While it’s not clear if these deaths were related to the drug, the manufacturer Biogen is investigating one particular case of a 75-year-old woman in Canada whose death is thought to be directly connected.
Earlier this month the European Medicines Agency’s advisory committee gave aducanumab a ‘negative trend vote’, suggesting that the drug will not be approved here (a formal ruling is expected in December).
Aducanumab is also not cheap — it costs $56,000 (nearly £40,000) a year, and there will probably be additional costs for monitoring patients with scans.
Yet still, experts are divided. While some say the drug should be available to those who need and want it, others argue it should never have been approved as it showed no meaningful benefit.
‘There was great hope for the amyloid-lowering drugs but the results from trials have been very disappointing,’ says Gill Livingston, a professor of psychiatry of older people at University College London.
It’s the condition many of us fear most, as the disease slowly but inexorably obliterates the mind
She says aducanumab’s approval in the U.S. ‘just shows how desperate people are for a drug. Many people would still take it despite the risks, because we have nothing else that promises to slow down brain decline’.
Another concern is that its approval sets a precedent for other drugs to be given the green light for Alzheimer’s even if they, too, don’t prove they can slow down brain decline and yet cause significant side-effects. This is highly probable because all of the frontrunners in the pipeline target the same pathway as aducanumab.
And some experts say millions more could be wasted targeting a mechanism that doesn’t yield benefits, when the focus should be shifted elsewhere, including to lifestyle changes we can all take to protect ourselves.
A MUCH HOPED-FOR BREAKTHROUGH
The need for a breakthrough in Alzheimer’s treatment is unequivocal. Around half a million Britons have the disease and the only available treatments, such as donepezil, rivastigmine and galantamine target brain chemicals to relieve symptoms, but usually become less effective as the condition worsens.
The problem is that we still don’t understand what causes Alzheimer’s. The conventional view is that amyloid-beta plaques build up and disrupt communication between nerve cells, ultimately causing them to die.
Based on this logic, the solution seems straightforward: clear the plaque to cure Alzheimer’s.
‘But aducanumab isn’t the transformative drug for Alzheimer’s as it generally had a small effect,’ says Dr Tom Russ, a consultant psychiatrist and director of the Alzheimer Scotland Dementia Research Centre at the University of Edinburgh, who was involved in the trials. ‘But Alzheimer’s is such an awful illness that anything which has an effect could be of value.’
Others argue that the clinical need justifies the level of risk. Dr Liz Coulthard, a dementia neurologist at North Bristol NHS Trust, who was also involved in aducanumab trials, explains: ‘Despite not meeting all of the clinical endpoints in its trials, aducanumab looks promising and I strongly believe we should approve it.
‘I understand reservations over the data, but we can’t shut down options for new Alzheimer’s drugs; we have to treat the right patients who may benefit from them.
‘For example, I see people of working age or in early retirement who have mild cognitive problems. This is a time where we could intervene to stop the condition worsening with the right treatment and yet we have no disease-modifying options for them.
‘They’d appreciate anything and should be able to decide whether to take this drug, knowing the potential benefit and risks.’
Some are more emphatic — Professor Bart De Strooper, director of the UK Dementia Research Institute, describes aducanumab as ‘a game changer’.
‘There is always a gamble you take when approving new therapies. But as we have seen during the Covid-19 pandemic, it is possible to move much faster than usual because of the clinical need for a treatment. Yet no one sees dementia as an acute problem, so there is no sense of urgency, which I disagree with.
‘Aducanumab is the first drug to have a significant effect on amyloid plaques. I think we’ll see greater benefits in subpopulations of patients, and timing is crucial.’
