For millions living with dementia – and their loved ones – the future can look bleak.
Thanks to medical breakthroughs, more people than ever survive our other biggest killers – heart disease, stroke, and cancer.
But research on dementia drugs has led to a dead end and hope has been destroyed time and time again.
Now there is finally cause for cautious optimism. There are plenty of exciting projects underway 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 got less during a trial, but the 67-year-old discontinued treatment last year when the trial was discontinued
Dr. John Skidmore of the Alborada Drug Discovery Institute in Cambridge, funded by Alzheimer’s Research UK, said: ‘We know that different types of dementia are caused by different disease processes. And because we understand the biology of those diseases, we have the opportunity to intervene. ‘
Last month, drug giant Biogen submitted its breakthrough treatment, called aducanumab, for approval in the U.S. after research findings showed that it could significantly slow the progression of Alzheimer’s disease, the most common form of dementia.
It means 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 and form so-called plaques in the brain. It is thought that in some people with Alzheimer’s disease, too many of these toxic plaques form, while in others, something happens that prevents the plaques from being washed away as they should.
Aducanumab, infused into the bloodstream, works by wiping these plaques to prevent damage.
An initial trial showed that it was safe, significantly reduced amyloid levels, and reduced the rate of cognitive decline. But the big disappointment came after a second, larger study, which started in 2017, was stopped abruptly for a year when an early analysis from one branch of the study suggested the drug was not working. But when Biogen analyzed all patients who received the highest doses for the longest time from both branches of the study, it found positive results.
There are plenty of exciting projects underway that could lead to 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, a dementia expert at University College Hospital in London, who led the UK branch of the Biogen study, said, “The research community is very cautious, although optimistic. Some people will mention what Biogen did data manipulation, and others will agree that it supports their original findings. But the fact is that there are people who believe they have achieved a fantastic result. ‘
One of those patients is retired dental surgeon Aldo Ceresa. The 67-year-old, who lives near Oxford with his wife Laura, was discontinued last year when the trial was discontinued. He hopes it will be restored now, saying that the drug “noticeably improves” his Alzheimer’s symptoms. Within a few months, he felt that his condition was no longer deteriorating. He also got better at the test leaders’ puzzles to assess his brain function. “I started to get pretty good at it,” he says. Laura noticed I was getting better too. I was less confused and able to concentrate better. ‘
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Since he stopped taking the drug, his condition has gotten worse, which is “frustrating,” he says.
“I know it won’t cure me, but it could give so many people so much extra time without their symptoms getting worse. Until approved, I eat healthy and keep my mind active by walking six miles a day and doing lots of puzzles. My former colleagues are surprised that despite the Alzheimer’s diagnosis in 2011 I am still doing so well. ‘
Dr. Mummery says the results of aducanumab prove that there is a link between the amount of amyloid in the brain and the rate of decline – which opens the door for the development of other drugs.
A decision by the American watchdogs may come as early as next year, and talks are underway 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 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 functioning of brain cells. These tangles are believed to develop later than amyloid plaques, and some scientists believe they may be a critical target for drugs in the later stages of the condition. Experts are now also trying to alter genes in the body’s cells, to knock out the processes that cause these proteins to form in the first place.
Last month, drug giant Biogen submitted its breakthrough treatment called aducanumab for approval in the U.S. (file photo of a Biogen facility in Cambridge, Massachusetts, U.S.)
A UK-led study by Dr. Mummery refers to a medicine known as an antisense oligonucleotide, or ASO, manufactured by the American pharmaceutical company Ionis. This targets the gene that produces tau. The drug is injected directly into the nervous system through the spine, and early studies have shown it to be safe. Further tests are needed to see how well it works.
“There are promising results when it comes to achieving the goal,” said Dr. Mummery. “All patients in the first trial want to continue. Tangles of tau develop later than amyloid plaques, so the hope is that we can intervene later in the disease and still see a difference. ‘
Scientists are also investigating whether the brain’s natural ability to clear excess amyloid proteins can be improved.
It’s important to develop new approaches together, says Dr. Skidmore. “Nobody alone is probably a magic bullet. Most people think it will be a combination of treatments that will work. ‘
The scientists make mini brains in a jar
Brains can only be properly examined after death if dementia has already caused damage.
This means that it is difficult to know what happens in the early stages of the disease.
But a team from University College London makes mini brains from skin samples. Selina Wray, professor of molecular neuroscience at University College London’s Institute of Neurology, who leads the study, said, “With these mini brains, we can look for the very first changes that occur in dementia.”
Any pea-sized mini brain, shown, can be used to study the development of dementia
To make the mini brain, skin cells are taken from volunteers and adapted in the lab to become stem cells – ‘building block’ cells that have the ability to transform into any type of tissue.
Scientists then use other chemicals to make brain cells, which naturally clump together.
Any pea-sized mini brain can be used to study the development of dementia. The volunteers who donated their cells all carry mutations in genes known to cause Alzheimer’s disease and frontotemporal dementia – a dementia that usually affects people ages 45 to 65. But none of them have any symptoms yet.
Prof Wray hopes the research will help scientists understand why no two people experience Alzheimer’s disease the same way, despite having the same genes.
“It can help explain why some people develop symptoms at age 50 and others at age 60,” she said.
“We can also start using medicines to see if we can bring the levels of proteins back to normal, and at what stage we need to intervene.”