Pioneering drug for dementia could be available in UK in two years
At last… the new drugs which could slow the march of this cruel disease: Pioneering treatment for dementia could be available in the UK in two years and pave the way for a new wave of therapies
- Last month, Biogen submitted the treatment, aducanumab, for approval in US
- Drug targets amyloid, a protein that builds up in brains of Alzheimer’s patients
- A decision from the American watchdogs could come as early as next year
- There may also be hope on horizon for patients with more advanced Alzheimer’s
For millions living with dementia – and for their loved ones – the future may appear bleak.
Thanks to medical breakthroughs, more people than ever are surviving our other biggest killers – heart disease, strokes and cancer.
But research into dementia drugs have led to dead ends, and time and again, hopes have been dashed.
Now, finally, there is cause for cautious optimism. A host of exciting projects are under way that could result in new medications for people with the disease and, perhaps, a new understanding of how it develops in the first place.
‘Noticeable improvement’: Aldo Ceresa with his wife Laura. His symptoms eased during a trial but 67-year-old had his treatment stopped last year when the trial was halted
Dr John Skidmore, of the Alborada Drug Discovery Institute in Cambridge, funded by Alzheimer’s Research UK, said: ‘We know different types of dementia are caused by different disease processes. And because we understand the biology of those diseases, it gives us a chance to intervene.’
Last month, drugs giant Biogen submitted its pioneering treatment, called aducanumab, for approval in the US after trial results showed it could significantly slow the progression of Alzheimer’s disease, the most common kind of dementia.
It means that the drug could be available in the UK in two years and pave the way for a new wave of therapies.
Aducanumab targets amyloid, a protein that builds up in the brains of Alzheimer’s patients. Normally these proteins circulate in the blood, but if they become sticky they can clump together, forming what are known as plaques in the brain. It is thought that in some people with Alzheimer’s, too many of these toxic plaques form, while in others something happens which stops the plaques being flushed away as they should.
Aducanumab, fed into the bloodstream via a drip, works by sweeping away these plaques to prevent damage.
An initial trial found it was safe, significantly reduced levels of amyloid and reduced the rate of cognitive decline. But huge disappointment came after a second, larger study, launched in 2017, was abruptly stopped a year in when early analysis of one branch of the trial suggested the drug was not working. But when Biogen analysed all patients given the highest doses for the longest amount of time, from both branches of the trial, it found positive results.
A host of exciting projects are under way that could result in new medications for people with the disease and, perhaps, a new understanding of how it develops in the first place (file photo)
Dr Catherine Mummery, dementia expert from University College Hospital, London, who led the UK arm of the Biogen trial, said: ‘The research community is very cautious, although optimistic. Some people will call what Biogen did data manipulation, and others will agree it supports their original findings But the fact is that there are people who believe they’ve had a fantastic result.’
One such patient is retired dental surgeon Aldo Ceresa. The 67-year-old, who lives with his wife Laura near Oxford, had his treatment stopped last year when the trial was halted. He hopes it will now be reinstated, as he says the drug ‘noticeably improved’ his Alzheimer’s symptoms. Within months, he felt his condition stopped deteriorating. He also got better at the puzzles set by the trial leaders to assess his brain function. ‘I was beginning to get quite good at them,’ he says. ‘Laura noticed I was getting better too. I was less confused and could concentrate better.’
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Since he stopped taking the drug, his condition has worsened, which has been ‘frustrating’, he says.
‘I know it’s not going to cure me, but it could offer so many people so much extra time without their symptoms progressing. Until it’s approved, I’m eating healthily and keeping my mind active by walking six miles a day and doing plenty of puzzles. My former colleagues are amazed I’m still doing so well despite being diagnosed with Alzheimer’s in 2011.’
Dr Mummery says the aducanumab results proves there is a link between the amount of amyloid in the brain and the level of decline – which opens the doors for other drugs to be developed.
A decision from the American watchdogs could come as early as next year, and discussions are said to be ongoing with the European Medicines Agency to license the drug on this side of the Atlantic.
There may also be hope on the horizon for patients with more advanced Alzheimer’s.
Another type of naturally occurring protein, called tau, normally helps the brain to function, but in advanced Alzheimer’s patients it can build up and form ‘tangles’.
When the tangles form, tau has the opposite effect, hindering the way brain cells work. These tangles are thought to develop later than amyloid plaques, and some scientists believe they could be a crucial target for drugs in the later stages of the condition. Experts are now also attempting to alter genes inside the body’s cells, to switch off the processes that cause these proteins to form in the first place.
Last month, drugs giant Biogen submitted its pioneering treatment, called aducanumab, for approval in the US (file photo of a Biogen facility in Cambridge, Massachusetts, US)
A study led in the UK by Dr Mummery involves a drug known as an anti-sense oligonucleotide, or ASO, produced by US pharma company Ionis. This targets the gene that produces tau. The drug is injected directly into the nervous system via the spine, and early trials have found it is safe. Further trials are needed to see how well it works.
‘There are promising results in terms of it meeting its target,’ Dr Mummery said. ‘Every single one of the patients in the first trial wants to continue taking it. Tangles of tau develop later than amyloid plaques, so the hope is we can intervene later in the disease and still see a difference.’
Scientists are also investigating whether the brain’s natural ability to clear away excess amyloid proteins can be improved.
It is important to develop new approaches in tandem, Dr Skidmore says. ‘None on their own are likely to be magic bullets. Most people think it will be a combination of treatments that will work.’
The scientists making mini-brains in a jar
Brains can only be properly examined after death when dementia has already done its damage.
This means it’s difficult to know what goes on in the early stages of disease.
But a team at University College London is creating mini-brains from skin samples. Selina Wray, professor of molecular neuroscience at University College London’s Institute of Neurology, who is leading the study, said: ‘With these mini-brains, we can look for the very earliest changes that are happening in dementia.’
Each pea-sized mini-brain, pictured, can be used to study the development of dementia
To make the mini-brains, skin cells are taken from volunteers, and modified in the laboratory so they become stem cells – ‘building-block’ cells that have the ability to transform into any type of tissue.
Scientists then use other chemicals to make them become brain cells, which naturally cluster together.
Each pea-sized mini-brain can be used to study the development of dementia. The volunteers who have donated their cells all carry mutations to genes known to cause Alzheimer’s disease and frontotemporal dementia – a dementia that usually affects people aged 45 to 65. But none of them has symptoms yet.
Prof Wray hopes the research will help scientists understand why no two people experience Alzheimer’s the same way, despite having the same genes.
‘It could help us explain why some people get symptoms at 50, and others at 60,’ she said.
‘We can also start using drugs to see if we can restore levels of proteins to normal, and at what stage we need to intervene to do that.’
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