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

Author

Listed:
  • Nir Lipsman

    (University of Toronto
    University of Toronto
    Sunnybrook Research Institute)

  • Ying Meng

    (University of Toronto
    University of Toronto)

  • Allison J. Bethune

    (University of Toronto
    Sunnybrook Research Institute)

  • Yuexi Huang

    (University of Toronto)

  • Benjamin Lam

    (University of Toronto
    University of Toronto)

  • Mario Masellis

    (University of Toronto
    University of Toronto)

  • Nathan Herrmann

    (University of Toronto
    University of Toronto)

  • Chinthaka Heyn

    (University of Toronto
    University of Toronto)

  • Isabelle Aubert

    (University of Toronto
    University of Toronto
    University of Toronto)

  • Alexandre Boutet

    (University of Toronto)

  • Gwenn S. Smith

    (Johns Hopkins University)

  • Kullervo Hynynen

    (University of Toronto
    University of Toronto
    University of Toronto)

  • Sandra E. Black

    (University of Toronto
    University of Toronto)

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.

Suggested Citation

  • 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 &, 2018. "Blood–brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04529-6
    DOI: 10.1038/s41467-018-04529-6
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    Cited by:

    1. Víctor A. Arrieta & Andrew Gould & Kwang-Soo Kim & Karl J. Habashy & Crismita Dmello & Gustavo I. Vázquez-Cervantes & Irina Palacín-Aliana & Graysen McManus & Christina Amidei & Cristal Gomez & Silpol, 2024. "Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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