Dementia research leads to potential new stroke treatment

The treatment trials have used experimental drugs to target a recently prescribed molecular pathway that damages the brain after a stroke.

Using pre-clinical animal models of ischaemic stroke, Dr Peng Lei and Professor Ashley Bush at Sichuan University in China and the Florey Institute of Neuroscience and Mental Health in Melbourne, have now shown that the tau protein, which stabilises the cellular ‘train track’ that transports molecules around cells, is also involved in stroke.

The tau protein transports iron out of brain cells, with lower tau levels leading to a build-up of iron in cells. This increase leads to brain cell death through a newly described molecular pathway called ferroptosis, which depends on iron.

Dr Lei and Professor Bush have published their new findings in Molecular Psychiatry, showing that tau levels are “markedly reduced” following a stroke.

“Excitingly we were able to intervene following stroke with five different experimental drugs designed to either lower iron levels, or block the ferroptosis pathway,” Dr Lei explains.

“Although all the treatments helped prevent brain damage, the ferroptosis-inhibiting drugs performed best, reducing the damaged area by more than half, with the animals functioning significantly better on tests of motor coordination and cognitive performance.”

Ischaemic strokes are caused by a blocked blood vessel, meaning the brain is starved of oxygen. They comprise 85 percent of all strokes in Australia, and acute treatment involves removing the blockage either by surgery or giving a clot-busting drug.

With, unfortunately, only 11 percent of stroke patients receiving this treatment in the prescribed time, and of those only half showing functional improvement, better treatments are urgently needed.

In the study, the ferroptosis-inhibiting drugs were delivered via the nose, which allowed their rapid, direct uptake by the damaged brain cells. This route and pathway, also means they could potentially be easily carried and administered by ambulance paramedics without the need for special brain scans or blood chemistry to be analysed.

As a result of the statistics and the findings in this new research, Stroke Foundation Clinical Council Chair, Associate Professor Bruce Campbell has welcomed the new avenue of research.

“This research is very interesting and opens another potential therapeutic avenue in the treatment of acute ischaemic stroke,” he says.

“The idea that iron may play a key role in ischaemic stroke is a fascinating insight and illustrates the sometimes unexpected benefits of research into fundamental mechanisms in biology that cross disease boundaries, in this case from dementia to stroke.”

He adds that Australian researchers are leading the way in innovative new stroke treatments such as this, but that stroke related research does not have enough funding despite its impact on so many Australians.

“There will be more than 56,000 new and recurrent strokes in Australia this year alone – that’s one every nine minutes,” he says.

“Stroke is one of Australia’s biggest killers and leading causes of disability.

“Despite shocking statistics and the devastating impact of stroke on the Australian community, stroke-related research is under represented nationally in Federal Government funding support.”

Given the lack of support and high statistics, Professor Campbell says the Stroke Foundation “welcomes evidence-based research to help prevent, treat and beat stroke”.