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December 05, 2019 — MedPage Today

By Ed Susman

In preliminary studies, focused ultrasound directed at the blood-brain barrier briefly made it more porous, which could be a means to allow drugs into Alzheimer’s patients’ brains or permit toxins to escape.

In the phase II safety trial, researchers treated three women diagnosed with Alzheimer’s disease with low-intensity focused ultrasound who had been administered a micro-bubble contrast agent to assess the safety of using the device and treatment.

“The results are promising,” said Rashi Mehta, MD, of West Virginia University (WVU) Medicine and West Virginia Clinical and Translational Science Institute in Morgantown. “We were able to open the blood-brain barrier in a very precise manner and document closure of the barrier within 24 hours. The technique was reproduced successfully in the patients, with no adverse effects,” she told MedPage Today at the Radiological Society of North America annual meeting here.

The treatment involved no administration of drugs designed to reduce the levels of amyloid plaque, one of the purported causative agents in Alzheimer’s disease. Mehta and co-researcher Jeffrey Carpenter, MD, also of WVU Medicine, suggested that just opening the blood-brain barrier might be helpful to Alzheimer’s patients because it could allow toxins to escape the confines of the brain and be eliminated by the body. In one patient who has been followed for more than a year, there has been no deterioration of function since undergoing the procedure.

For the new study, the researchers delivered low-intensity focused ultrasound to specific sites in the brain critical to memory in women, ages 61, 72, and 73, with early-stage Alzheimer’s disease and evidence of amyloid plaques. The women underwent three successive treatments at 2-week intervals, and were tracked for bleeding, infection and edema, or fluid buildup.

Post-treatment brain magnetic resonance imaging (MRI) confirmed that the blood-brain barrier opened within the target areas immediately after treatment. Closure of the barrier was observed at each target within 24 hours. Mehta suggested that the blood-brain barrier was probably open only for about 6-8 hours, but the patients were examined for closure of the barrier 24 hours after the treatment.

For the procedure, the researchers performed MRI-guided low-intensity focused ultrasound, positioning a helmet over the patient’s head while in the scanner. The helmet is equipped with approximately 1,000 separate ultrasound transducers angled in different orientations. Each transducer delivers sound waves targeted to a specific area of the brain. Patients also receive an injection of contrast agent made up of microscopic bubbles. Once ultrasound is applied to the target area, the bubbles oscillate.

“The helmet transducer delivers focal energy to specified locations in the brain,” Mehta explained. “Oscillation of the microbubbles causes mechanical effects on the capillaries in the target area, resulting in a transient loosening of the blood-brain barrier.”

“This is a very elegant technique,” commented Max Wintermark, MD, chief of neuroradiology at Stanford University Medical School in California, who was not involved with the study. “You inject microbubbles in the bloodstream and then with magnetic resonance imaging you identify your target and then you aim focused ultrasound at this target and the ultrasound shakes the microbubbles against the walls of the arteries, which makes the arteries of the blood-brain barrier open up. And even more interesting is that this opening is reversible.”

“You can imagine a lot of conditions for which this may be useful,” Wintermark told MedPage Today. “We have a lot of great medications for treating diseases in the brain, but we cannot get the medications there. This technique may give us the opportunity to have these drugs pass through the blood-brain barrier.”

Wintermark said the technique can specifically target which areas of the blood-brain barrier can be opened so as to target specific areas of the brain that require therapy.

“Sometimes you want to get medications into the brain, and sometimes you want to get toxins out, and I think that is what they are doing in this application for Alzheimer’s disease,” he said.

Mehta and colleagues are recruiting additional patients for the phase II study, which eventually will include 10 patients. The team will then design a phase III study to prove the treatment’s effectiveness.

“We’d like to treat more patients and study the long-term effects to see if there are improvements in memory and symptoms associated with Alzheimer’s disease,” Mehta said. “As safety is further clarified, the next step would be to use this approach to help deliver clinical drugs.”

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