Treating Alzheimer’s Disease With Ultrasound

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Scientists at the West Virginia University Rockefeller Neuroscience Institute are winners of the 2024 Gizmodo Science Fair for their research into using ultrasound to improve the effectiveness and safety of Alzheimer’s disease drugs.

The question

Is it possible to boost the potency of today’s anti-amyloid antibody medications for Alzheimer’s disease, the most common form of dementia?

The results

In a first-in-human trial of three patients published in January, the team found that its ultrasound technique in combination with anti-amyloid antibody medications appeared to speed up the removal of hardy amyloid beta plaques from the brains of people with mild Alzheimer’s disease.

Why they did it

Gsf2024 Award Alzheimers
© Vicky Leta/Gizmodo

The build up of misfolded and hardy amyloid beta in the brain is thought to be one of the key drivers of Alzheimer’s, which affects around 7 million Americans today. Scientists have developed many lab-made antibodies that can break down amyloid, but it’s only recently that some of these drugs have shown enough success in clinical trials to win regulatory approval. To date, however, these approved medications only seem to have a modest effect on improving people’s symptoms and slowing down the rate of cognitive decline.

WVU scientists have been looking into the potential benefits of using focused ultrasound on the brain for years, with their Alzheimer’s research in people dating back to 2018. This research had already shown that low-intensity bursts of ultrasound alone could loosen the blood-brain barrier and potentially knock loose bits of amyloid plaque from the brain. But with the advent of newer drugs, the team wanted to see if combining the two methods could work better than either alone at clearing amyloid.

Why they’re a winner

The team’s focused ultrasound technique is designed to safely disturb the blood-brain barrier, a shield that protects the brain from infections and other dangers—but one that also limits most drugs from easily reaching the brain.

People undergoing the ultrasound procedure are monitored via MRI while wearing a helmet that deploys low-intensity bursts of ultrasound at certain blood vessels passing through the brain. Doctors then administer microscopic air bubbles that travel along these blood vessels. When the ultrasound hits these bubbles, they temporarily expand and open up the blood-brain barrier for a short time. During that brief window, patients can receive what should be more potent anti-amyloid treatment.

“If we can open the blood-brain-barrier non-invasively and temporarily using ultrasound, that can provide a window of opportunity where now we can do a targeted delivery of the drug payload into the areas of the brain that need it specifically,” said Ali Rezai, project leader and executive chair of the Rockefeller Neuroscience Institute. “And after the procedure, the blood-brain barrier will reseal and regain its protective functionality within 48 hours.”

This method could not only improve the effectiveness of anti-amyloid drugs but possibly make them safer, since people might be able to take them over a shorter period of time than currently prescribed (a few months compared to two years, Rezai believes). One real concern about anti-amyloid drugs is their risk of causing potentially life-threatening brain bleeding.

What’s next

Rezai and his team plan to start a new, larger trial of the combination treatment this year, which will use a more potent anti-amyloid medication (the original study used the antibody aducanumab, which has since been discontinued) and target a bigger area of the brain. They hope to show evidence that the therapy can both accelerate plaque clearance as well as improve people’s cognitive health. They also expect to expand their efforts outside of WVU, working with scientists and patients at other research sites.

While this research is still early, the applications of focused ultrasound could extend even beyond Alzheimer’s. “Now that the brain-blood barrier can be overcome safely, that opens up many [treatment] possibilities, in my opinion—for brain tumors, for Alzheimer’s, Parkinson’s, and many other areas,” Rezai said.

The team

The January study involved the collaboration of more than a dozen scientists across different fields from West Virginia University and Vanderbilt University. And as the research expands, Rezai expects many more to join in.

“I would say at least 100 people from different fields and different institutions are working together on this. We have colleagues in Europe. We have colleagues across the U.S. We have neurosurgeons, neurologists, psychiatrists, psychologists, brain imaging specialists, PET scan specialists, MRI specialists, MRI, physics, biomedical engineers, all working together in this research,” Rezai said. “It is really multidisciplinary specialists collaborating together, along with the public and private sector. Collaboration is critical because without that, it’ll be difficult to tackle these big public health problems like Alzheimer’s.”

Click here to see all of the winners of the 2024 Gizmodo Science Fair.



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