Focused Ultrasound Opens Blood-Brain Barrier, May Aid Alzheimer's Treatment

By Reuters Staff

December 09, 2019

NEW YORK (Reuters Health) - MRI-guided low-intensity focused ultrasound (LIFU) can safely open the blood-brain barrier (BBB) and allow for targeted delivery of drugs in patients with Alzheimer's disease (AD), according to new preliminary research.

Studies in animals have shown that LIFU can reversibly open the BBB, reduce beta-amyloid plaque burden, improve memory and allow for targeted drug and stem-cell delivery. A phase-1 proof-of-concept clinical trial demonstrated safe and temporary opening of the BBB with LIFU in the dorsolateral prefrontal cortex in five patients with AD.

This week at the Radiological Society of North America's annual meeting in Chicago researchers reported initial results of a phase-2 trial currently in progress evaluating the safety and efficacy of BBB opening within the hippocampus and entorhinal cortex at sites of abnormal amyloid burden in patients with early AD.

Three women with early AD and evidence of amyloid plaques received three successive treatments at two-week intervals.

MRI of the brain confirmed BBB opening within the target areas immediately after treatment, with closure of the barrier within each target site evident within 24 hours, the researchers said.

"The results are promising," study co-author Dr. Rashi Mehta of West Virginia University, in Morgantown, and West Virginia Clinical and Translational Science Institute said in a conference news release.

"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," said Dr. Mehta.

With MRI-guided LIFU, a helmet equipped with more than 1,000 separate ultrasound transducers is placed over the patient's head after they are positioned in the MRI scanner. Each transducer delivers sound waves targeted to the target areas. 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. Oscillation of the microbubbles causes mechanical effects on the capillaries in the target area, resulting in a transient loosening of the blood-brain barrier," Dr. Mehta explains in the release.

"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. As safety is further clarified, the next step would be to use this approach to help deliver clinical drugs," she added.

Dr. Mehta was unable to provide comment by press time.

SOURCE: Radiological Society of North America 2019 Annual Meeting.