A novel nasal spray developed by a team led by researchers at the University of Texas Medical Branch (UTMB) has been shown to get rid of disease proteins in mouse models of Alzheimer’s disease (AD).
A single dose of this innovative nasal spray was found to significantly reduce tau protein buildup in aged mice with an Alzheimer-like condition. This was reported in a study that appeared in the journal Science Translational Medicine.
Findings offer some hope that this sort of therapy may one day help millions of people with Alzheimer’s and other forms of dementia.
Role of tau proteins in Alzheimer’s
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Neurofibrillary tangles that are linked to neurodegenerative diseases such as AD mainly compose of a protein known as tau. Tau proteins help to stabilize the internal structure of neurons in the brain. They aid in stabilizing microtubules in axons, supporting the shape and arrangement of nerve cells.
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Tau proteins are not a problem until they start forming tangles. AD and other neurodegenerative disorders only result when tau starts to mutate and fold aberrantly.
Toxic tangles are usually present along with plaque buildup in Alzheimer’s patients. Tangles form within neurons while plaques develop between brain cells. This inhibits proper neuronal function, leading to cognitive decline.
Efforts by scientists to keep harmful tau proteins from building up in the brain have not yielded much. This is largely due to the reduced ability to infiltrate the intracellular sections.
Nasal spray keeps toxic tangles in check
The UTMB researchers identified an antibody that was capable of binding to and doing away with tau proteins. The antibody called tau conformation-specific monoclonal antibody-2 (TTCM2) was enclosed in tiny lipid bubbles that were small enough to cross the blood-brain barrier. In the brain, the bubbles gave way to release the antibodies.
The team turned the antibody bubbles into a nasal spray. When this was used on mouse models, researchers found that the animals showed fewer symptoms of dementia.
This finding may also be interpreted as cognition improving in the mice.
Post-mortem testing showed that the levels of tau tangles and folds reduced and there were fewer tau seeds. Interestingly, researchers also observed similar effects when they tested their nasal spray on human nerve tissue samples.
What makes the nasal spray promising?
Until now, scientists have struggled to come up with Alzheimer’s treatments that can breach the blood-brain barrier. The approach used – that is, delivering therapy through the nose – aided in skirting this barrier. This ensures faster and better absorption by the brain.
The nasal therapy not only aims to reduce toxic tau proteins in the brain but also to block the production of the so-called “tau seeds.” This prevents the spread of dysfunctional tau through the brain.
However, this breakthrough nasal spray is still a long way from being available to people with Alzheimer’s. There is next a need to work out its suitability for human testing. It is only after that can human trials follow. But it’s probably something to be hopeful about considering the groundbreaking treatment delivery method.
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References
Sagar Gaikwad et al (2024). Nasal tau immunotherapy clears intracellular tau pathology and improves cognitive functions in aged tauopathy mice. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.adj5958
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