Science

Alzheimer’s-preventing nasal spray targets novel brain mechanism

Alzheimer’s-preventing nasal s...
A nasal spray has been developed to inhibit a brain mechanism hypothesized to be an early driver of Alzheimer's disease
A nasal spray has been developed to inhibit a brain mechanism hypothesized to be an early driver of Alzheimer's disease
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A nasal spray has been developed to inhibit a brain mechanism hypothesized to be an early driver of Alzheimer's disease
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A nasal spray has been developed to inhibit a brain mechanism hypothesized to be an early driver of Alzheimer's disease

An international team of researchers has reported on the successful preclinical tests of a novel nasal spray developed to prevent neurodegeneration associated with Alzheimer’s disease. The treatment was effective at reversing the pathological signs of Alzheimer’s in mouse models and the researchers are looking to start human tests in two years.

The prevailing hypothesis driving most Alzheimer’s disease research is the idea that neurodegeneration is caused by the abnormal accumulation of amyloid and tau proteins in the brain. So the majority of pharmaceutical interventions over recent decades have focused on reversing, or preventing, those toxic protein aggregations.

But virtually every one of these novel drugs has failed at some stage of human trials. And many big pharmaceutical companies have pulled out of the Alzheimer’s drug development field altogether, putting the research into the “too-hard” basket.

This new research, published in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions, comes from a biotech company called Neuro-Bio. The company was formed in 2013 by Oxford University neuroscientist Susan Greenfield, building off decades of work investigating the origins of Alzheimer’s disease.

Neuro-Bio’s research is based on the idea that a successful Alzheimer’s disease treatment must target mechanisms that precede the accumulation of amyloid and tau in the brain. It is suggested that once these toxic proteins are seen to be building up in the brain and causing neuronal damage it is too late to try and stop or reverse the process with drugs.

The alternative hypothesis underpinning Neuro-Bio’s work is the idea that a brain chemical known as T14 may be one of the earliest pathological drivers of Alzheimer’s disease. T14 is a molecule crucial to brain development in early life but it is suspected to become toxic in later life.

Prior studies have indicated an early pathological sign of Alzheimer’s could be toxic levels of T14 in a part of the brainstem called the isodentritic core. Neuro-Bio hypothesizes inactivating T14 in that brain region could prevent the cascade of neurological events that ultimately lead to Alzheimer’s disease.

“By using basic neuroscientific knowledge we have identified what we believe is an underlying mechanism driving Alzheimer’s disease in the brain, and have developed a molecule (NBP14) to combat it,” explained Greenfield.

The newly published study reports on preliminary animal experiments testing a nasal spray formulation of NBP14 in mouse models of Alzheimer’s disease. The promising findings show six weeks of NBP14 use led to a decrease in brain amyloid levels in the mice, and after 14 weeks the animals displayed cognitive improvements similar to normal healthy controls.

The results consistently indicate that NBP14 might interfere with the neurotoxic process that leads to neuronal degeneration in Alzheimer’s,” said Paul Herrling, non-executive director of Neuro-Bio. “This work has very exciting implications for treating Alzheimer’s because it is based on a strong scientific theory that hasn’t yet been applied to treatment of the disease.”

Alongside T14 inhibition serving as a possible treatment, it is hypothesized T14 measurements in blood or skin could potentially act as an early diagnostic tool. Neuro-Bio said in a statement it believes testing for abnormal T14 levels could identify early neurodegenerative processes that precede Alzheimer’s symptoms by 10 or 20 years.

These findings are inarguably promising, pointing to a potential future where a few short nasal sprays every morning could be a preventative treatment for Alzheimer’s disease. But that scenario is still a distant prospect, with the researchers indicating there is at least two years of work before the experimental drug can even begin human testing.

Beyond that point, assuming everything goes well, this kind of treatment is at least 10 years away from real-world applications. And it is worth remembering that the history of Alzheimer’s research is littered with promising animal studies that did not translate well to humans.

But these findings are as good as one could hope at this stage, and Neuro-Bio said there were no harmful side effects generated by the therapeutic doses in their animal studies to date.

“Our recent efficacy study in mouse models further validates previous work describing an erstwhile unidentified process in neurodegeneration and offers very exciting prospects for treating the disease in humans,” said Greenfield. “This research should help position the drug intercepting this process, NBP14, for human clinical trials and hopefully create an entirely new era of Alzheimer’s therapeutics.”

The new study was published in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions.

Source: Neuro-Bio

6 comments
6 comments
BogBeast
Treatment for Alzheimer's can't come soon enough. The current drain on health resources is nothing compared to what will come in the future, promising treatments such as this should be fast-tracked and funded as well as the covid vaccine was..
Kpar
Well said, BogBeast.
BlueOak
“And many big pharmaceutical companies have pulled out of the Alzheimer’s drug development field altogether, putting the research into the “too-hard” basket.”

That’s a pretty major failure by big Pharma.

… and yet they’ll be the first to claim their brand solved the problem after one of these smaller startups solves it… by buying and absorbing the successful startup.
ljaques
+1 to BogBeast and BlueOak.
Now everyone pray that this testing works out and they have all these delights come true: early testing, early prevention, and total cures for the blasted Alz beast.
Smokey_Bear
I disagree with BogBeast - Progress on this should push forward at a normal pace, you don't pull funding (R&D) from one thing, and push harder on another.
I know Alzheimer's is terrible, I remember my grandma had it (~15 years ago), she would call me the wrong name, and eventually would stare right through me, like I wasn't even there.
But are you going to tell the girl with a brain tumor, sorry, we pulled funding on your cure/treatment, to cure/treat Alzheimer's...
human trails in 2 years is great, I wish them nothing but the best. I just don't like the short sighted thinking of people like BogBeast.
He's from the same crowd of people who think we shouldn't explore space, when we have problems here on Earth.
Or so & so (Steve Jobs, Elon Musk, insert name here) is great, they should be President! Which is stupid, they found where they excel, and you want them to do something completely different.
Sorry for the rant, but no, it should not be fast tracked.
Ralf Biernacki
@Smokey: Your position is supported by heart-wringing emotional appeal---the poor girl with a brain tumor, how moving! But in RL, the Alzheimer research is not being outcompeted for funding by brain cancer research, but by far more important cash cows like weight-reduction pills and male pattern baldness treatments. Once you confront that, the argument for fast-tracking is much harder to dismiss.