New Alzheimer’s nasal spray clears toxic tangles in human neurons, mice : ScienceAlert

Twisted and confused proteins are found in the brains of many people who die from Alzheimer’s disease.

Some scientists suspect that these ganglia can damage and even kill brain cells. So far, however, drugs used in clinical trials to target the ganglia have had little success.

A promising new drug has now been introduced by an international team led by researchers at the University of Texas. The nasal spray can bypass the blood-brain barrier and destroy tangles of tau proteins in living mice. The drug also works to clear away tangles within and between human neurons in the lab.

The drug is specifically designed to recognize and destroy the most toxic forms of tau proteins, such as those found in some cases of Alzheimer’s and dementia.

But that wasn’t the only challenge. Researchers also had to figure out how to get the drug past the blood-brain barrier and into brain cells.

Neuroscientist Sagar Gaikwad and his team decided to package the drug in tiny bubbles that could slip past cell membranes. By injecting the drug into the noses of mice, they were able to bypass the blood-brain barrier.

In older mice with tau-associated brain disease, a single spray was enough to clear toxic tau from the brain. Two weeks later, the mice showed improved cognitive function.

Of course, this does not mean that the drug will have the same effect on humans.

In an overview of the findings for Science Translational MedicineNeuroscientists Soraya Meftah, Claire Durrant and Tara Spiers-Jones of the University of Edinburgh, who were not involved in the current research, note that while many tau-based therapies show promise in animal models, their translation into effective drugs for humans “has so far failed.”

Much work remains to be done, but the initial results from Gaikwad and his colleagues are promising.

In experiments using postmortem human brain tissue donated by patients with Alzheimer’s disease, Lewy body dementia and Pick’s disease (a form of frontotemporal dementia), the new antibody drug not only cleared away the tau tangles but also stopped the release of “tau seeds,” which tangle proteins into other parts of the brain via connected neurons.

“Many open questions remain, including whether this treatment, administered intranasally in humans, allows the antibody to penetrate our much larger brains in effective doses and whether there are potentially dangerous side effects, such as inflammation, which is a concern in all studies of amyloid-targeted immunotherapy,” Meftah, Durrant and Spiers-Jones write.

“Despite these limitations, this is an important piece of work.”

Gaikwad and his colleagues hope their technique will lead to further research into the treatment of tau-associated diseases.

The research was published in Science Translational Medicine.

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