Nasal Spray may Delay the Alzheimer’s by Removing Toxic Plaques

Current Alzheimer's medications can help with some symptoms, but novel disease-modifying treatments are not generally available. Recently, researchers created a nasal spray that reduces inflammation and removes protein accumulation in Alzheimer's disease in a mouse model. The spray may slow the progression of Alzheimer's disease by up to 15 years, according to the researchers.
There are various types of dementia, but the most common is Alzheimer's, which accounts for up to 70% of cases [1]. Monoclonal antibody therapy, such as lecanemab and donanemab, were the first Alzheimer's disease-modifying drugs.
They remove beta-amyloid plaques, which are hallmarks of Alzheimer's, potentially putting off cognitive signs. However, the cost of the treatments is high, and some specialists worry that the risks of adverse consequences might exceed the advantages.
In a recent study, researchers at Texas A&M University College of Medicine employed a nasal spray to target astrocytes and microglia, cells that cause neuroinflammation or inflammation of the brain, slowing Alzheimer's progression in a mouse model.
They proposed that the spray could postpone the onset of Alzheimer's disease by up to 15 years if similar outcomes are confirmed in humans. Journal of Extracellular Vesicles published this research [2].
Spray targets the hyperactive immune cells in the brain.
Astrocytes and microglia are crucial players in the neuroinflammation associated with Alzheimer's disease. They protect neurons (nerve cells) and eliminate damaged nerve tissue in healthy brains. However, in Alzheimer's, they become overactive and kill nerve cells after initially removing beta-amyloid plaques.
The researchers used a mouse model of early-stage Alzheimer's disease to administer a nasal spray that contained an anti-inflammatory medication made from stem cells in extracellular vesicles.
Targeting these immune cells was the goal to lessen inflammation and the accumulation of toxic proteins in the brain.
They administered two doses of the nasal spray containing the medication, or a placebo spray, one week apart to the 3-month-old mice, which included both wild-type and genetically altered (or transgenic) mice to exhibit Alzheimer's-like symptoms.
The quantity and activity of microglia and astrocytes were measured by euthanizing five mice 72 hours following the second injection.
The researchers put the remaining mice through behavioral tests three weeks following the second treatment. They conducted similar tests again regularly throughout the subsequent month to track the mice's cognitive performance after treatment. They euthanized the mice and examined their brains.
Spray therapy reduced inflammation and improved cognitive function.
In this mouse model, untreated transgenic mice typically exhibit beta-amyloid plaques, elevated microglial activity, and inflammation when they are 4.5 months old.
Nevertheless, at 4.5 months, the mice in this study who received the nasal spray treatment exhibited fewer microglial clusters and less activation of genes linked to neuroinflammation. Furthermore, compared to the untreated mice, they showed fewer beta-amyloid plaques.
The hippocampus, the part of the brain that is most important for learning and memory and is heavily damaged by Alzheimer's, showed the most noticeable reduction in inflammation.
Both male and female treated mice outperformed the untreated mice in behavioral tests in terms of mood and cognitive performance.
What’s next?
Reducing microglial activity may reduce their beneficial effects, but this was not observed when mice were given nasal spray.
According to a press release from the study's authors, ingesting extracellular vesicles derived from neural stem cells altered the gene expression of microglia. It also decreased the number of dangerous proinflammatory proteins without impairing the microglia's capacity to continue removing the protein accumulation linked to Alzheimer's disease [3].
Ashok K. Shetty, the corresponding author of the study, has applied for a patent on the intranasal delivery of extracellular vesicles produced from neural stem cells for the treatment of neurological conditions, including Alzheimer's. According to him, the National Institute on Aging-funded research at his lab has already sparked additional research. If effective, he expects that treatment will be able to postpone Alzheimer's-related changes and serious cognitive problems by 10 to 15 years after the initial diagnosis.
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