A first of its kind drug that tackles toxic protein tangles in the brain in Alzheimer’s patients could provide fresh hope millions living with the disease.
Developed by a team of international researchers led by British experts, the drug tackles two ‘hotspots’ of a protein that leads to the memory-robbing condition getting worse over time.
While drugs targeting these proteins have been developed before, they typically only work on one of these areas, not both.
Development is still in the early stages with the medication only having been tested on human cells in the lab and on animals.
But the experts behind the drug, called RI-AG03, say initial findings are promising.
Developed by a team of international researchers led by British experts, the drug, called RI-AG03, tackles two ‘hotspots’ on the protein that leads to the memory robbing condition getting worse over time. Stock image
The medicine targets tau proteins which normally play a crucial role in maintaining brain cell health.
However, in people with Alzheimer’s disease, they clump together and form clumps that starve brain cells of nutrients and slowing down signals in the organ.
These tangles eventually kill neurons and as more die, memory and thinking ability become increasingly impaired.
This is where RI-AG03 comes in. Professor Amritpal Mudher, an expert in neuroscience at the University of Southampton, explained it targets two parts of the tau protein where these clumps originate.
‘For the first time, we have a drug which is effective in inhibiting both these regions,’ she said.
By inhibiting these parts of the tau protein from working the clumps are less likely to form, reducing their build-up in the brain and slowing down the progression of the disease.
It works on a different mechanism to recent blockbuster Alzheimer’s drugs lecanemab and donanemab, which recruit the immune system to clear the build-up of another harmful protein linked to the disease called amyloid.
Dr Anthony Aggidis, also at Southampton, and author of a new paper on RI-AG03 , added that the discovery could provide hope to the millions suffering from Alzheimer’s.
‘Our research represents an important step toward creating treatments that can prevent the progression of diseases like Alzheimer’s disease,’ he said.
‘By targeting both of the key areas on the tau protein, this unique approach could help address the growing impact of dementia on society, providing a much-needed new option for treating these devastating diseases.’
The team, which also included experts from the US and Japan, have published the results of experiments with the drug in the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Alzheimer’s disease is the most common cause of dementia. The disease can cause anxiety, confusion and short-term memory loss
These involved giving RI-AG03 to fruit flies with toxic tau protein tangles.
Researchers found the drug not only suppressed the degeneration of the insects’ brain cells but also extended their lifespan by two weeks compared to those not given the medication.
Professor Mudher said: ‘The higher the dosage given, the greater the improvement we saw in the fruit fly’s lifespan.’
The team also carried out experiments in human cells in the lab and found similar evidence it reduced tau clumping.
They said they now plan to carry out further studies in rodents and, if successful, launch clinical trials in humans.
Research on RI-AG03 was funded by charity the Alzheimer’s Society UK.
Its associate director of research and innovation Dr Richard Oakley welcomed the results.
‘Dementia is the UK’s biggest killer, and it applies enormous cost and pressure to our healthcare system which is why we’re committed to funding world leading studies like this one,’ he said.
‘This research is taking promising steps towards a new one-of-a-kind therapy.
‘This drug has the potential to be more targeted than others currently being studied, and we hope it will result in fewer toxic side effects.
‘It’s important to note that the study is in its early stages, so we don’t yet know if it will work or be safe for humans, but it’s an exciting development and we look forward to seeing where it leads.’
According to the Alzheimer’s Society, about 982,000 people in the UK are living with dementia.
Around 900,000 Brits are currently thought to have the memory-robbing disorder. But University College London scientists estimate this will rise to 1.7million within two decades as people live longer. It marks a 40 per cent uptick on the previous forecast in 2017
The figure is expected to rise to 1.4 million by 2040.
After years of false starts into potential Alzheimer’s drugs there has been a flurry of medications show promise.
Last year, the medical world rejoiced as the first drug to clearly slow the progression of Alzheimer’s was approved in the US.
Manufacturers said trial results showed lecanemab – also known as Leqembi – slowed cognitive and functional decline in early-stage Alzheimer’s patients by 27 per cent over 18 months.
This is the equivalent of a five-month slowdown in the progression of the disease.
It was followed by results for donanemab which trails showed slowed progression of Alzheimer’s by as much as 35 per cent.
But experts have warned that people who take the drugs actually lose volume in their brains.
There have also been concerns about brain bleeds among patients.
Trial results for lecanemab show that around 21 per cent of participants who received the drug experienced brain swelling or bleeding, compared to 9 per cent of those who received a placebo.
The majority of patients had no side effects, or had very mild symptoms, while most who experienced brain swelling or bleeding saw these issues resolve by the end of the trial.
Experts have also previously highlighted how more than 80 per cent of Brits at risk of Alzheimer’s could miss out on the new drugs due to a lack testing for the disease.
Scientists from London estimated just 14 per cent of patients referred to clinics were actually likely to benefit from the treatments.
Researchers said there was a ‘clear and urgent’ need to improve NHS screening to work out who may benefit from new Alzheimer’s drugs.
Alzheimer’s is the leading cause of dementia, triggering the memory robbing disorder in about three in five patients.
Dementia cases are expected to sky-rocket in the coming years in part because of an increasing ageing population.
Currently, the only available drugs for Alzheimer’s are to treat its symptoms.
