New study is a promising ‘first’ in Alzheimer’s drug development

For the first time, scientists have created a drug that works by targeting both key areas of a protein linked to the disease.

The study found that the medication, called RI-AG03, was effective at preventing the build-up of Tau proteins in both laboratory and fruit fly studies.

Lead author Dr Anthony Aggidis, former postdoctoral research associate at Lancaster University and visiting researcher at the University of Southampton, said: “Our research represents an important step toward creating treatments that can prevent the progression of diseases like Alzheimer’s disease.

“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.”

Tau proteins help to stabilise the internal skeleton of nerve cells (neurons) in the brain.

But in Alzheimer’s disease, these proteins malfunction, clumping together to form tangles which clog the neurons.

This stops them from getting the nutrients and signals they need to survive.

As more neurons die, memory, thinking, and behaviour become increasingly impaired, leading to the cognitive decline seen in Alzheimer’s.

Researchers say there are two hotspots of the Tau protein where this clumping tends to happen.

And although current treatments target one or the other of these hotspots, the new drug uniquely targets and blocks both.

Amritpal Mudher, professor of neuroscience at the University of Southampton, said: “For the first time, we have a drug which is effective in inhibiting both these regions.

“This dual-targeting mechanism is significant because it addresses both domains that stimulate Tau aggregation, potentially paving the way for more effective treatments for neurodegenerative diseases like Alzheimer’s.”

When tested in fruit flies, the drug suppressed damage to the neurons, and extended the lives of the flies by around two weeks – a significant extension given the life span of the insects.

In order to make sure this was not unique to fruit flies, researchers at the University of Texas Southwestern Medical Centre tested the drug in a type of living human cell in a laboratory.

According to the findings the drug successfully penetrated the cells and reduced the build up of Tau proteins.

The researchers now plan to test the drug in rodents, before moving on to clinical trials.

They believe their work will have a significant impact on drug discovery efforts in the field of neurodegenerative diseases.

Dr Richard Oakley, associate director of research and innovation at Alzheimer’s Society UK, which funded the study, said: “This research is taking promising steps towards a new one-of-a-kind therapy which targets Tau, a damaging protein in the brains of people living with Alzheimer’s, preventing it from clumping together.

“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.

“Research will beat dementia, but we need to make it a reality sooner through more funding, more partnerships, and more people taking part in dementia research.”

The research, published in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, was led by Lancaster University in collaboration with the University of Southampton, Nottingham Trent University, Tokyo Metropolitan Institute of Medical Science and the University of Texas Southwestern Medical Centre.