A nasal spray to reverse brain aging sounds like a big claim. Researchers at Texas A&M University say their early findings point that way, after an experimental treatment restored memory, reduced chronic inflammation and improved brain cell function after just two doses.
The study was led by Dr Ashok Shetty, university distinguished professor and associate director of the Institute for Regenerative Medicine, with senior research scientists Dr Madhu Leelavathi Narayana and Dr Maheedhar Kodali. The findings were published in the Journal of Extracellular Vesicles.
“Brain age-related diseases like dementia are a major health concern worldwide,” Shetty said. “What we’re showing is brain aging can be reversed, to help people stay mentally sharp, socially engaged and free from age-related decline.”
The treatment uses extracellular vesicles, or EVs, microscopic biological particles that naturally transport genetic material between cells. Researchers loaded them with microRNAs, molecules that help regulate biological processes in the brain.
“Brain age-related diseases like dementia are a major health concern worldwide. What we’re showing is brain aging can be reversed, to help people stay mentally sharp, socially engaged and free from age-related decline.”
Dr. Ashok K. Shetty
University Distinguished ProfessorTexas A&M University Naresh K. Vashisht College of Medicine
“MicroRNAs act like master regulators,” Narayana said. “They help modulate and regulate many gene and signaling pathways in the brain.”
Researchers delivered the EVs through a nasal spray, which they said allowed the treatment to bypass the brain’s protective barrier and travel directly into brain tissue.
“The mode of delivery is one of the most exciting aspects of our approach,” Kodali said. “Intranasal delivery allows us to reach, and treat, the brain directly without invasive procedures.”
According to the researchers, the treatment targeted immune cells involved in chronic inflammation and suppressed inflammatory systems including the NLRP3 inflammasome and the cGAS-STING signaling pathways, which are linked to age-related brain inflammation.
Scientists also found the treatment restored activity in mitochondria, the structures inside cells responsible for producing energy. They said aging and inflammation can damage mitochondria, leaving brain cells less efficient and more vulnerable to decline.
“We are giving neurons their spark back by reducing oxidative stress and reactivating the brain’s mitochondria,” Narayana said.
The researchers said behavioural testing showed treated models performed significantly better on memory and recognition tasks than untreated controls. They were more successful at identifying familiar objects, recognizing new ones and detecting changes in their surroundings.
“We are seeing the brain’s own repair systems switch on, healing inflammation and restoring itself,” Shetty said.
The effects appeared quickly and lasted for months after only two doses, the researchers said.
“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,” Shetty said.
The findings may matter as dementia cases rise in the United States. Annual cases are expected to increase from roughly 514,000 in 2020 to around 1 million by 2060, according to the summary released by Texas A&M University.
“The trend signals a pressing need for policies and innovative interventions that can minimize both the risk and severity of neurodegenerative disorders like dementia,” Shetty said.
The study also found similar treatment responses across both sexes.
“It’s universal,” Shetty said. “Treatment outcomes were consistent and similar across both sexes.”
The research was supported by the National Institute on Aging, and the team has filed a US patent related to the therapy. The paper is titled Intranasal Human NSC‐Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS‐STING Signalling, in Aged Hippocampus.
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