Blood–brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound

Nir Lipsman (), Ying Meng, Allison J. Bethune, Yuexi Huang, Benjamin Lam, Mario Masellis, Nathan Herrmann, Chinthaka Heyn, Isabelle Aubert, Alexandre Boutet, Gwenn S. Smith, Kullervo Hynynen and Sandra E. Black
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Nir Lipsman: University of Toronto
Ying Meng: University of Toronto
Allison J. Bethune: University of Toronto
Yuexi Huang: University of Toronto
Benjamin Lam: University of Toronto
Mario Masellis: University of Toronto
Nathan Herrmann: University of Toronto
Chinthaka Heyn: University of Toronto
Isabelle Aubert: University of Toronto
Alexandre Boutet: University of Toronto
Gwenn S. Smith: Johns Hopkins University
Kullervo Hynynen: University of Toronto
Sandra E. Black: University of Toronto

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood–brain barrier, and reduce beta-amyloid and tau pathology in animal models of Alzheimer’s disease. Here, we used focused ultrasound to open the blood–brain barrier in five patients with early to moderate Alzheimer’s disease in a phase I safety trial. In all patients, the blood–brain barrier within the target volume was safely, reversibly, and repeatedly opened. Opening the blood–brain barrier did not result in serious clinical or radiographic adverse events, as well as no clinically significant worsening on cognitive scores at three months compared to baseline. Beta-amyloid levels were measured before treatment using [18F]-florbetaben PET to confirm amyloid deposition at the target site. Exploratory analysis suggested no group-wise changes in amyloid post-sonication. The results of this safety and feasibility study support the continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer’s disease.

Date: 2018
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DOI: 10.1038/s41467-018-04529-6

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