First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound
Open accessAbstract
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.
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- Authors
- Abrahao, A., Meng, Y., Llinas, M., Huang, Y., Hamani, C., Mainprize, T., Aubert, I., Heyn, C., Black, S. E., Hynynen, K., Lipsman, N., & Zinman, L.
- Affiliations
- Sunnybrook Health Science Centre (CA)
- ORCID
- Venue
- Nature Communications
- Published
- 2019-09-26
- Volume
- 10
- Issue
- 1
- Pages
- 4373-4373
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6763482
- OpenAlex
- W2976433890
- Cited by
- 476
- References
- 3
- Citations by year
- 2026: 25 · 2025: 57 · 2024: 76 · 2023: 71 · 2022: 87 · 2021: 90 · 2020: 67 · 2019: 2
- FWCI
- 21.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- ALS Society of Canada
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- amyotrophic lateral sclerosis, blood-brain barrier opening, MR-guided focused ultrasound, primary motor cortex, targeted drug delivery, brain drug delivery, feasibility and safety
- MeSH terms
- Aged, Amyotrophic Lateral Sclerosis, Blood-Brain Barrier, Brain, Feasibility Studies, Female, Fentanyl, Humans, Magnetic Resonance Imaging, Male, Midazolam, Middle Aged, Prospective Studies, Ultrasonography, Drug Delivery Systems, Anesthetics, Intravenous
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