Scientists at Texas A&M University have created a nasal spray that, in mice, lowers brain inflammation and recovers memory abilities that had been lost.
The team says that, following additional research and development, comparable effects may be possible in people.
Nasal spray targets neuroinflammaging
The treatment is aimed at "neuroinflammaging": localised areas of persistent stress in the ageing brain. This process is associated with cognitive decline linked to age and is believed to contribute to neurological conditions including Alzheimer's. The scientists liken neuroinflammaging to sections of an engine that are continually overheating.
In mouse models, the spray addressed these areas using millions of minute biological sacs called extracellular vesicles (EVs). Produced from human stem cells, the EVs carry proteins and genetic instructions.
The animals were 18 months old, an age generally considered older adulthood in mouse research and broadly equivalent to people in their late 50s to late 60s.
"As we develop and scale this therapy, a simple, two-dose nasal spray could one day replace invasive, risky procedures or maybe even months of medication," says neuroscientist Ashok Shetty.
"It's universal. Treatment outcomes were consistent and similar across both sexes."
EV treatment for hippocampal inflammation
The researchers concentrated on microglia, the brain's immune cells, within the hippocampus. This area is essential for learning and memory and is a site of substantial neuroinflammation.
Healthy stem cells, which are capable of growing and developing into other types of cell, are now being extensively explored for their therapeutic possibilities. It has also been shown that stem-cell by-products, including EVs, can deliver much of the benefit while being safer to introduce into the body.
For the study, male and female mice aged 18 months were given two intranasal doses at an interval of two weeks.
Administering the treatment via the nose could allow EVs to access the brain more directly, without invasive surgery. The researchers say the vesicles were absorbed rapidly.
Following both doses, treated mice performed better than control animals in tests of object recognition and spatial memory. Additional biochemical examination of the hippocampus indicated that the treatment produced the intended effects on brain inflammation.
MicroRNAs restore brain cell function
EVs contain microRNAs, small fragments of genetic code that control gene expression. Once released, these microRNAs reprogramme brain cells, switching off or reducing some of the alarm signals responsible for neuroinflammaging.
For ageing mice, this enabled microglia to return to a more typical state, including in the way their mitochondria, the cells' energy systems, handled energy.
"MicroRNAs act like master regulators. They help modulate and regulate many gene and signaling pathways in the brain," says neuroscientist Madhu Leelavathi Narayana.
"We are giving neurons their spark back by reducing oxidative stress and reactivating the brain's mitochondria."
New cases of dementia in the US alone could reach one million annually by 2060, twice today's level. The study therefore highlights a potential new approach to limiting age-related neuroinflammation, which can trigger dementia.
Separate animal research has indicated that related EV treatments could also support recovery after a stroke or brain injury.
Clinical trials in humans will be required to establish whether these treatments can address conditions such as mild cognitive impairment, although the initial findings are encouraging.
The results add to an expanding body of work on healthier ageing, with less of the biological deterioration normally brought by advancing age.
"Brain age-related diseases like dementia are a major health concern worldwide," says Shetty.
"We're aiming for successful brain aging: keeping people engaged, alert, and connected. Not just living longer, but living smarter and healthier."
The research was published in the Journal of Extracellular Vesicles.
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