New human trials out of West Virginia University offer a promising path for treating Alzheimer's disease by using high-frequency sound waves.
Alzheimer’s is the most common form of dementia. The national Alzheimer’s Association estimates that 6.7 million Americans over age 65 have the disease, which destroys memory and other cognitive skills.
The leading theory is that Alzheimer's is related to the abnormal build-up of a sticky protein called amyloid in the brain. The results of a new class of drugs — anti-amyloid monoclonal antibodies — support this. Alzheimer’s patients who receive infusions of these medications see both a reduction of amyloids and a modest slowing of the disease’s progression.
Overall, the benefits of these new Alzheimer's medications have been limited due to the blood-brain barrier. The protective membrane shields the brain from toxins and pathogens circulating in the blood: Unfortunately it also blocks most pharmaceuticals.
It seems West Virginia scientists were able to make these monoclonal antibodies more effective by breaching this roadblock using ultrasound to create a temporary hole in the blood-brain barrier.
The study was published last week in the New England Journal of Medicine, and involves three research volunteers who have mild Alzheimer’s. Each was injected with microbubbles which then circulated in their blood streams. Then researchers used ultrasound’s high-frequency waves that targeted small areas of volunteers’ brains. This caused the bubbles to expand, which stretched the blood vessels in the blood-brain barrier forcing it to open temporarily — thus allowing the medication to reach the amyloids.
Though the sample size is too small to draw definitive conclusions, these preliminary results are exciting, said senior author Marc Haut of West Virginia’s Rockefeller Neuroscience Institute. All three research participants had a reduction in amyloids and did not suffer any severe side effects.
Haut said his team’s next step is to use ultrasound on a larger area of the brain, “Although we were very successful in these areas that we targeted, it's really a small amount of the brain and the overall amyloid load in the brain.”
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The use of ultrasound as a treatment for neurological diseases is a growing field of study and an example of how that research can be repurposed for Alzheimer’s, said Rebecca M. Edelmayer, senior director of scientific engagement for Alzheimer’s Association.
In 2021, researchers in Canada used ultrasound and microbubbles to deliver an antibody therapy to patients whose breast cancer had metastasized to the brain. And a May 2023 study from Northwestern University used a similar protocol to enhance the effectiveness of chemotherapy drugs to treat glioblastoma tumors.
Human trials from West Virginia University have a strong scientific premise that offers an interesting proof-of-concept, said Dr. Gil Rabinovici. Rabinovici is director of the University of California, San Francisco's Alzheimer’s Disease Research Center and not affiliated with the study.
Rabinovici notes the West Virginia researchers didn’t test the ultrasound protocol in people who have the APOE e4 gene, which is found in 65-70% of Alzheimer’s patients. People with this gene have a higher risk of brain swelling when they undergo anti-amyloid monoclonal antibody treatment.
“It really is unknown whether focused ultrasound would increase the risk of developing this potentially serious side effect,” said Rabinovici.
Pilot trials are important for mapping out the next steps in research, said Dr. Sanjeev Vaishnavi, who studies neurodegenerative diseases at the University of Pennsylvania, Perelman School of Medicine. He is not affiliated with the West Virginia study.
“Anything we can do to try to push the field forward and use the new tools to try to better deliver these new therapies, I think is helpful for us,” said Vaishnavi.
Edelmayer, Racbinovici and Vaishnavi all said the pilot’s results were intriguing and warranted a bigger study that has more research participants. That’s welcomed news to senior author Marc Haut who is looking for collaborators so he can test the protocol on a larger scale.
But Haut cautions that people should not pin their hopes on his team: “There have been many attempts in the past to treat this disease. It looked promising and then they failed.”
Still, he’s optimistic and he thinks the general public should be as well. In the past few years there’s been marked progress when it comes to Alzhiemer’s drugs and adding ultrasound might be a winning combination.
