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 body’s blood-brain barrier, which keeps foreign substances, including medications and immunotherapies, from fully reaching the brain.
Since 2015, a group of researchers at Australia’s 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, they’re 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.
Alzheimer’s 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 Alzheimer’s 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 (contrast agents) 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.
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, they’re 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.
It’s 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 doesn’t involve toxic protein build-ups, has a different pathology and will thus require different treatment strategies.”
Earlier this year, the Australian government granted $10 million in new funding to Götz’s 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 isn’t 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 Alzheimer’s. She was able to return home the day after her treatment.
It’s 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? We’d like to hear your thoughts in the comments below.
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