British scientists are using ground-breaking stem cell technology to grow ‘mini-brains’ in a laboratory to test a host of potential new treatments for Alzheimer’s disease.
The organ-like collections of cells allow researchers to observe for the first time how dementia begins in the brain.
In an exclusive interview with The Mail on Sunday, the lead researcher behind the project, Selina Wray, professor of molecular neuroscience at Alzheimer’s Research UK and senior research fellow at University College London (UCL), revealed that they were now testing 96 drugs.
“We are entering an exciting new era of dementia research,” she says. ‘With the help of these mini-brains, we may be able to develop treatments that could stop the onset of dementia or even reverse its effects.’
The need for new treatments for dementia is clear: almost a million Britons live with the degenerative disease which causes memory loss, confusion and the inability to carry out simple tasks. By 2050, this figure is expected to double as the UK population ages.
Selina Wray, professor of molecular neuroscience at Alzheimer’s Research UK and senior research fellow at University College London (UCL), leads the groundbreaking breakthrough
By 2050, an estimated two million Britons could be suffering from Alzheimer’s disease and other forms of dementia
The problem for scientists is that it is virtually impossible to observe changes in the brain while a patient is still alive. This is because, unlike other organs, scientists cannot remove part of the brain to study it in a laboratory.
‘The brain does not regenerate, so if we were to remove a tissue sample we would permanently damage it,’ says Prof Wray. ‘Brain scans are useful for giving a general idea of what’s going on, but they can’t tell you what’s going on at the molecular level.
‘Most research into the impact of dementia on the brain has been done with the brains of people who have died from the disease. But if the brain is already damaged, it is very difficult to find out what started the degeneration in the first place.’
To create the mini brain, researchers collect skin samples from patients with a genetic form of dementia. They are born with errors in their DNA, which means they develop the disease at a young age.
Using specialized drugs, the scientists can convert the skin cells into stem cells – which can develop into different cell types – that can be manipulated to become brain cells. About three million of these – all from the same patient – are then combined to create a mini-brain the size of a pencil rubber.
Prof Wray says: ‘We are at the point where we have witnessed these dementia changes in the mini-brain and we can start to look at what we can do to prevent the damage.’
The past 12 months have brought glimmers of hope for dementia patients, with the drugs lecanemab and donanemab becoming the first treatments ever to successfully slow the condition.
However, both carry a high risk of serious side effects: about one in six lecanemab patients and about a quarter of those given donanemab suffered brain hemorrhages. Three patients in each trial also died due to side effects related to the drugs. And the treatments are only effective if they are given to patients in the very early stages of Alzheimer’s disease. This is especially problematic because there is no effective tool – such as a blood test – to diagnose the disease before symptoms begin.
Crucially, neither drug reverses the symptoms of Alzheimer’s disease.
‘(Lecanemab and donanemab) are exciting because they prove it is possible to slow dementia,’ says Prof Wray. ‘But to be truly successful in curing the disease, you need to target it from the very beginning, before the disease can progress further.’
Experts have a number of possible theories about the cause of dementia. Many believe it is caused by a toxic protein called amyloid. These normally circulate in the brain until destroyed by the immune system, but for unclear reasons they can clump together in dementia patients to form plaques, disrupting cell function and causing brain damage.
The new Alzheimer’s drugs target amyloid plaque, but cannot reverse previous damage.
Although it may be at least a decade before any of these experimental drugs can be offered to patients, Prof Wray says she is optimistic about the future for patients.
“Hopefully the next step will be drugs that have the same impact as lecanemab and donanemab, but without the side effects,” she says.
‘In the future, with the help of research on these mini-brains, we may reach a point where it is possible to reverse the damage.’
- Professor Selina Wray will give a talk, ‘Building a brain in a dish: how can stem cells help us to understand dementia?’, at New Scientist Live at ExCeL, London, on 8 October 2023. To book tickets, visit live.newscientist.com.