Aduhelm May Be More Effective at Treating Alzheimer’s Disease When Combined with Ultrasound

There has been a great deal of controversy recently surrounding the newly FDA-approved Alzheimer’s drug Aduhelm (aducanumab), with some experts claiming it is likely ineffective. However, a team of researchers believes they may have the answer to improving its efficacy.

The FDA did express concerns over the lack of evidence for the effectiveness of the new drug, but the agency went ahead and granted its approval anyway, with the caveat that Biogen must conduct a “phase 4” trial after the drug goes on the market. After this several-years-long trial is complete, the FDA will decide whether or not to rescind its approval.

In the meantime, the injectable IV drug will be available to the general public as the first FDA-approved Alzheimer’s drug in about 20 years. In fact, it is one of only six drugs for the disease currently approved for use in the U.S.

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However, Professor Jürgen Götz of the Queensland Brain Institute and his colleagues may have just the thing to make Aduhelm more effective for Alzheimer’s patients. Back in 2015, the team conducted a study on mice and found that ultrasound waves were successful at removing beta-amyloid plaques from the mice’s brains. Beta-amyloid is believed to be a contributor to Alzheimer’s disease when it is allowed to build up in the brain and form plaques that interrupt the communication of neurons.

The team also found that, when combined with intravenously injected microbubbles, ultrasound waves relaxed the blood-brain barrier, which in turn activated microglia to digest amyloid proteins, effectively reversing the neurological damage caused by the plaque buildup.

“We have shown that tau (the second Alzheimer’s pathology) is cleared by a second mechanism, neuronal autophagy. When microbubbles are not overdosed, the procedure is safe,” says Götz.

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In a later study, published in May of 2021, Götz and his colleagues used ultrasound scans combined with microbubbles to substantially improve memory, in addition to several other related neurological and physiological processes, in “physiologically aged, senescent mouse brain[s].”

“Advanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation, an electrophysiological correlate of memory,” read the study. “We conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.”

In April, the team suggested that adding Aduhelm to the mix might make the treatment even more effective and more likely to work well for human subjects. They’re hoping another study can be done to combine the ultrasound-microbubble co-treatment with a dose of Aduhelm to test whether it might be an opportunity to turn back the clock on Alzheimer’s disease.

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Götz believes humans might require “more than one and less than 10” treatments sessions in a one- or two-week period to see results. Of course, further studies will be necessary to show whether this treatment has similar results in human subjects as it does in mice, as well as to determine its safety. “A lot depends on how early in the disease process [Alzheimer’s] is diagnosed and that one treats early,” says Götz.

For the sake of the future of Alzheimer’s treatment, we hope that the researchers are able to find a treatment combination that shows good results in clinical trials and reverses the neurological damage done by the disease. We’ve gone too long without a good treatment for Alzheimer’s disease, and we’re so glad to see so many people working hard to change that!

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