First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound
Agessandro Abrahao (),
Ying Meng,
Maheleth Llinas,
Yuexi Huang,
Clement Hamani,
Todd Mainprize,
Isabelle Aubert,
Chinthaka Heyn,
Sandra E. Black,
Kullervo Hynynen,
Nir Lipsman and
Lorne Zinman
Additional contact information
Agessandro Abrahao: University of Toronto
Ying Meng: University of Toronto
Maheleth Llinas: Sunnybrook Research Institute
Yuexi Huang: University of Toronto
Clement Hamani: University of Toronto
Todd Mainprize: University of Toronto
Isabelle Aubert: University of Toronto
Chinthaka Heyn: University of Toronto
Sandra E. Black: University of Toronto
Kullervo Hynynen: University of Toronto
Nir Lipsman: University of Toronto
Lorne Zinman: University of Toronto
Nature Communications, 2019, vol. 10, issue 1, 1-9
Abstract:
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.
Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12426-9
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DOI: 10.1038/s41467-019-12426-9
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