Ultrasound Treatment For Alzheimer’s

A New Treatment Approach

On June 7, the FDA approved the first Alzheimer’s disease drug in nearly two decades. Aducanumab, a drug developed by Biogen, is an antibody designed to targetand reduce amyloid plaques. The drug has already sparked immense enthusiasm and controversy. Proponents say the drug is a much-needed start in the fight against the disease, but others argue that the drug doesn’t substantially improve cognition. They say the approval could open the door to the FDA greenlighting more Alzheimer’s drugs that don’t have a clear benefit, giving false hope to both patients and their families.

Konofagou’s ultrasound approach could potentially boost the effects of drugs like aducanumab. “Our technique can be seamlessly combined with aducanumab in early Alzheimer’s, where it has shown the most promise, to further enhance both its amyloid load reduction and further reduce cognitive deficits while using exactly the same drug regimen otherwise,” she says. For the Columbia team, the goal is to use ultrasound to maximize the effects of aducanumab, as they’ve done with other drugs in animal studies.

But Konofagou’s approach could transcend drug controversies, and even drugs altogether. The big promise of ultrasound is that it could eventually make drugs for Alzheimer’s obsolete.

Minorities Hit the Hardest

Scientists Are Harnessing Sound Waves In Hopes Of Treating Alzheimers

Researchers at Columbia University are testing an experimental treatment for Alzheimer’s that uses ultrasound waves and “microbubbles.”

In 2010, a 67-year-old former executive assistant for a Fortune 500 company was diagnosed with mild cognitive impairment. By 2014, her doctors confirmed she had Alzheimer’s disease.

As her disease progressed, she continued to live independently but wasn’t able to drive anymore. Today, she can manage most of her everyday tasks, but her two daughters are considering a live-in caregiver. Despite her condition, the woman may represent a beacon of hope for the approximately 44 million people worldwide living with Alzheimer’s disease. The now 74-year-old is among a small cadre of Alzheimer’s patients who have undergone an experimental ultrasound procedure aimed at slowing cognitive decline.

In November 2020, Elisa Konofagou, a professor of biomedical engineering and director of the Ultrasound and Elasticity Imaging Laboratory at Columbia University, and her team used ultrasound to noninvasively open the woman’s blood-brain barrier. This barrier is a highly selective membrane of cells that prevents toxins and pathogens from entering the brain while allowing vital nutrients to pass through. This regulatory function means the blood-brain barrier filters out most drugs, making treating Alzheimer’s and other brain diseases a challenge.

An Ultrasound Therapy For Dementia

Alzheimers disease and some other dementias are marked by protein plaques and tangles in the brain. Immunotherapy treatments have been studied for years as a potential way to break down and remove those proteins. The problem is that so few of those antibodies make it through the blood-brain barrier. With better access to the brain, researchers think, immunotherapy could reduce symptoms and improve memory in Alzheimers patients. Ultrasound on its own may be effective, too.

Professor Jürgen Götz heads the Clem Jones Centre for Ageing Dementia Research at the Queensland Brain Institute and his team has been testing the effects of injecting patients with microbubbles and then using ultrasound on the brain to briefly open the blood-brain barrier. In an email, Götz describes how the combination of microbubbles and ultrasound therapy works.

Ultrasound causes intravenously injected microbubbles to oscillate, thereby exerting a subtle pressure on the walls of blood vessels such that they transiently open the tight junctions.

This opening allows injected immunotherapy agents to enter the brain and activate certain brain cells that take in and digest harmful proteins.

Their research has also found that ultrasound on its own can kickstart the brain to clear out some of plaques and tangles, but that ultrasound plus immunotherapy is more effective than either alone.

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Innovative Use Of Ultrasound Technology

Researchers Gerhard Leinenga and Jurgen Gotz reported the results of an innovative approach to treating Alzheimers in the Science Translational Medicine journal ). Though researchers hesitate to use the word breakthrough, it is difficult to not be extremely hopeful. The researchers used ultrasound waves to break apart the amyloid plaques that are the cause of Alzheimers symptoms like memory loss and decline in cognitive functioning.

The experiments were conducted in an Alzheimers Disease mouse model. The ultrasound waves, directed at the brains plaque clumps, activated microglial cells. These cells digested and cleared amyloid plaques that interfere with brain synapses. The ultrasound waves temporarily unsealed the blood-brain barrier and improved memory.

In the past, potential treatments failed to safely penetrate the blood brain barriers endothelial walls. Now ultrasound has been able to open the barrier which then triggered the microglial cells. They do not know all the whys of the reported activity, but it is hoped that this will become a safe treatment for Alzheimers patients.

Looking Forward To The Future

Just being able to open the blood brain barrier was found to have therapeutic effects. The tricky next steps will be determining how to safely use the procedure in aging adults who may have compromised blood brain barriers. It is hoped that the Leinenga and Gotz research project leads to great strides being made in the treatment of Alzheimers disease. The benefits of using ultrasound include:

• Ultrasound is inexpensive compared to other types of treatments
• It is non-invasive

Read Also: The Course Of Alzheimer’s Disease

A Potential Ultrasound Treatment For Alzheimers

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How It Works: Punching Little Holes In The Barrier

First, its helpful to know that focused ultrasound isnt new to medicine: Its already used to treat symptoms of other neurodegenerative conditions like essential tremor and Parkinsons disease. The experimental technique thats being explored in clinical trials for Alzheimers, however, is different.

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• Taking care of your mental health
• Managing your blood sugar

I think the most important thing that weve been showing is that this seems to be very safe and well tolerated, Kaplitt says.

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Fitting Into The Future Of Medicine

Rezai and Kaplitt arent the only researchers pursuing focused ultrasound for Alzheimers treatment. A handful of other U.S.-based institutions are studying the approach, and so are Canadian researchers. At the same time, scientists are looking at a myriad of technologies, targets and therapies that could potentially hold the answer or at least part of one to treating Alzheimers. Its likely going to be a combination of treatments that will ultimately be effective at staving off some of the cognitive impairment of aging, the Mayo Clinics Petersen says.

Its not clear whether ultrasound will fit into that mix, but Rezai is optimistic that it will play a role in how we treat brain diseases in the future. It opens up a whole new set of opportunities for us as physicians and scientists to explore not only for Alzheimers, but for other neurological conditions, he says.

Rachel Nania writes about health care and health policy for AARP. Previously she was a reporter and editor for WTOP Radio in Washington, D.C. A recipient of a Gracie Award and a regional Edward R. Murrow Award, she also participated in a dementia fellowship with the National Press Foundation.

More on health

Researchers Are Studying How The Technology Can Impact Dementia And The Brain

Imagine strapping on a high-tech helmet, lying on an MRI table and, after microbubbles bounce in your blood vessels and ultrasound waves are beamed at your brain, walking away with fewer symptoms of Alzheimers disease.

That may sound like its straight out of a science fiction movie, but its not. Whats called focused ultrasound technology is just one of the many avenues scientists are exploring in an ongoing quest to find a treatment for the most common type of dementia.

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We need to really explore and be bold in terms of the way were looking at Alzheimers, because the disease is not going away, its increasing, says neurosurgeon Ali Rezai, M.D., executive chair of the Rockefeller Neuroscience Institute at West Virginia University and a leading researcher on the topic.

In fact, the number of people living with dementia, including Alzheimers disease, globally is expected to nearly triple by 2050, a new study published in The Lancet predicts. Cases in the U.S. could increase from nearly 5.3 million to about 10.5 million during that same time.

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Could A New Ultrasound Therapy Treat Dementia

The effort to find effective treatments for dementia has been called one of the most intractable problems in medicine, according to the New York Times. One reason progress is so difficult is that the bodys blood-brain barrier, which keeps foreign substances, including medications and immunotherapies, from fully reaching the brain.

Since 2015, a group of researchers at Australias University of Queensland has been working with ultrasound to temporarily open the blood-brain barrier so antibody treatments can get in and harmful dementia-related proteins can be cleared out. Now, theyre planning a phase one clinical safety trial in humans later this year. Read more about ultrasound therapy and how it can be used to treat dementia.

Cautious Progress For Possible Dementia Treatment

Götz and his researchers studied ultrasound therapy in mice and observed an improvement in memory function and a reversal of dementia symptoms in the mice after treatment. Because brains become more fragile with age, the team made a point of testing the treatment on older mice who were the equivalent of 80-90 in human years. In early 2018, they reported that the ultrasound procedure did not cause damage or increase bleeding in geriatric mice.

The scientists have also tested the process for safety on larger brains, in sheep. Now, theyre planning to conduct a small clinical trial later this year to evaluate the safety of the ultrasound treatment in humans.

If that trial shows that the ultrasound therapy is safe, they can move forward with trials to see if the treatment is effective for humans.

Its too early to know whether this approach will prove safe in humans, but if it does, it could eventually make ultrasound a viable tool for removing plaques and tangles in people with dementia, with or without the addition of immunotherapy agents.

Götz says of the treatment, The treatment is designed as a potential therapy for dementia and targets the toxic protein build-ups that are a hallmark of this condition. Vascular dementia, which doesnt involve toxic protein build-ups, has a different pathology and will thus require different treatment strategies.

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Trial Of Ultrasound Treatment For Alzheimers Underway

13 December 2022

Image: The University of Queensland

Image: The University of Queensland

A pioneering treatment for Alzheimerâs disease, developed at The University of Queensland, is being tested in a small safety trial underway in Brisbane.

The safety trial – with a limit of 12 participants – is the culmination of a decade of ongoing research led by Professor Jürgen Götz at UQâs Queensland Brain Institute .

Professor Götz said the study was an important step to determine whether the ultrasound could be safely delivered, following pioneering discoveries about its potential use to improve memory function.

Professor Jürgen Götz. Image: The University of Queensland

âThere is currently no effective treatment for Alzheimerâs, so it is hugely rewarding that we could in the future potentially treat the disease with ultrasound,â Professor Götz said.

The 12-month trial is being conducted at Mater Hospital Brisbane and UQ and is being overseen by researcher and neurologist, Professor Peter Nestor.

Professor Peter Nestor. Image: The University of Queensland

âWeâre treating an area at the back of the brain that is affected early in the course of Alzheimerâs disease,â Professor Nestor said.

âEach participant receives four treatments which will be administered fortnightly, and after completing the course, theyâll have an MRI scan of the brain and a repeat cognitive test.â

Professor Jürgen Götz. Image: The University of Queensland

Meet Judi Polak Alzheimer’s Patient And Star Of A Clinical Trial Showing Promising Results

by Hallie Levine, AARP, December 11, 2019

WVU Medicine

Judi Polak with members of the team from the Rockefeller Neuroscience Institute at the WVU School of Medicine

En español | Almost 6 million Americans live with Alzheimer’s, a devastating disease for which there is no known cure. Judi Polak, 62, is one of them. She’s also one of the much smaller number of people who’ve signed on to let researchers experiment on their ailing brains in her case, having ultrasound energy beamed into her hippocampus, the brain’s memory center.

Perhaps surprisingly, Judi didn’t think twice about joining the groundbreaking clinical trial, which she describes as part of her active fight against the disease she was diagnosed with four years ago. We all have a lot of inner strength, Judi says of her family . One of our good friends said that the first person to be cured with Alzheimer’s is alive today. That became our mantra and fight song. I choose not to suffer, not to die, but to fight.”

It’s a fitting motto for a woman whose husband describes her as a butterfly on acid. Before Judi’s diagnosis, I’d joke that Judi didn’t just burn the candle on both ends she set fire to the middle, Mark says.

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Judi and Mark Polak

One of our good friends said that the first person to be cured with Alzheimer’s is alive today. That became our mantra and fight song. I choose not to suffer, not to die, but to fight.

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Clearing The Brain Of Memory Barriers

According to Alzheimers Disease International, there are an estimated 44 million people around the world who suffer with dementia, of which Alzheimers is one form. The debilitating disease has been undergoing intensive research in an effort to pinpoint its causes. Much has already been learned about Alzheimers, and each new discovery puts science one step closer to finding a reliable treatment. With the latest research reported in Australia, it appears that ultrasound waves will be the treatment of the future, offering hope to millions of people.

So far, medical researchers believe most Alzheimers Disease is the result of one of two conditions in the brain:

• Amyloid plaques These plaques are found between the neurons. In an Alzheimers patient, clusters of beta-amyloid molecules clump together. The formation of a sticky protein plaque cluster impedes brain functioning.
• Neurofibrillary tangles The neurofibrillary tangles are located inside the brains neurons. In this situation, defective tau proteins clump together to form a dense insoluble mass. The mass causes microtubules to get twisted, impeding the transport of critical nutrients and substances in the brain.

How Can Ultrasound Help

The research is still in the early stages, but studies so far show that low-intensity ultrasound waves targeted at specific regions of the brain can safely open the blood-brain barrier a roadblock of sorts that prevents toxins, germs and other substances in the bloodstream from entering the brain tissue. And temporarily opening the barrier in areas of the brain associated with Alzheimers disease could give researchers a new way to deliver drugs and therapeutics straight to the source.

Most of the things that are really cutting-edge and interesting, like gene therapies and cell therapies, require you to directly inject them into the brain, says Michael Kaplitt, M.D., a neurosurgeon and vice chair for research at Weill Cornell Medicine, who has worked with Rezai on focused ultrasound research. What if you could do this without brain surgery?

Its also possible that opening the blood-brain barrier could be helpful on its own, though more research is needed. Rezai, Kaplitt and a team of researchers found that clinical trial participants in the early stages of Alzheimers disease saw a modest reduction in beta-amyloid plaques sticky protein clumps that impair communication between neurons and are one of the hallmarks of Alzheimers.

Also Check: How To Know If It’s Dementia Or Alzheimer’s

What Happens Next

Earlier this year, the Australian government granted $10 million in new funding to Götzs project. Phase one of the clinical trial later this year will include about 10 subjects. If this phase shows that it is safe, researchers will conduct two more phases of the trial to investigate the effectiveness of the ultrasound therapy.

Australia isnt the only country where ultrasound treatments for dementia are under study, however. In 2018, scientists in Toronto reported the results of their phase one safety trial to temporarily open the blood-brain barrier and researchers at West Virginia University performed a phase two ultrasound trial on a woman with Alzheimers. She was able to return home the day after her treatment.

Its too soon to know if treatments for people with dementia might come out of this research, but for an intractable problem like this, finding a way to safely open the blood-brain barrier could be the first step toward a solution.

Do you have a parent or senior loved one with dementia? Would your loved one be willing to use ultrasound therapy for dementia treatment? Wed like to hear your thoughts in the comments below.

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