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First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound

Author

Listed:
  • Agessandro Abrahao

    (University of Toronto
    University of Toronto
    Sunnybrook Research Institute)

  • Ying Meng

    (University of Toronto
    Sunnybrook Research Institute
    University of Toronto)

  • Maheleth Llinas

    (Sunnybrook Research Institute
    University of Toronto)

  • Yuexi Huang

    (University of Toronto)

  • Clement Hamani

    (University of Toronto
    Sunnybrook Research Institute
    University of Toronto)

  • Todd Mainprize

    (University of Toronto)

  • Isabelle Aubert

    (University of Toronto
    University of Toronto)

  • Chinthaka Heyn

    (University of Toronto
    University of Toronto)

  • Sandra E. Black

    (University of Toronto
    University of Toronto
    University of Toronto
    University of Toronto)

  • Kullervo Hynynen

    (University of Toronto
    University of Toronto
    University of Toronto
    University of Toronto)

  • Nir Lipsman

    (University of Toronto
    Sunnybrook Research Institute
    University of Toronto)

  • Lorne Zinman

    (University of Toronto
    University of Toronto)

Abstract

MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS.

Suggested Citation

  • Agessandro Abrahao & Ying Meng & Maheleth Llinas & Yuexi Huang & Clement Hamani & Todd Mainprize & Isabelle Aubert & Chinthaka Heyn & Sandra E. Black & Kullervo Hynynen & Nir Lipsman & Lorne Zinman, 2019. "First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12426-9
    DOI: 10.1038/s41467-019-12426-9
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    Cited by:

    1. Mahdi Derayatifar & Mohsen Habibi & Rama Bhat & Muthukumaran Packirisamy, 2024. "Holographic direct sound printing," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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