Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease.
Authors: Rezai AR, D'Haese PF, Finomore V, Carpenter J, Ranjan M, Wilhelmsen K, Mehta RI, Wang P, Najib U, Vieira Ligo Teixeira C, Arsiwala T, Tarabishy A, Tirumalai P, Claassen DO, Hodder S, Haut MW
Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aβ) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aβ was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography. Cognitive tests and safety evaluations were conducted over a period of 30 to 180 days after treatment. (Funded by the Harry T. Mangurian, Jr. Foundation and the West Virginia University Rockefeller Neuroscience Institute.).
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To evaluate the safety and efficacy of ultrasound-mediated blood–brain barrier opening combined with aducanumab treatment in patients with Alzheimer's disease.
Animal model / Human subject
Human; 77-year-old man; 59-year-old man; 64-year-old man
Disease model
Alzheimer's Disease
MRI or image guidance method
MRI-guided
Targeted brain region(s)
Frontal Lobe; Parietal Lobe; Temporal Lobe; Hippocampus
Cargo name and characteristics
Aducanumab — human monoclonal IgG1 antibody targeting aggregated beta-amyloid (protein, monoclonal antibody)
Route of administration
Intravenous
Outcomes and Safety
Summary of Outcomes
MRI-guided focused ultrasound BBB opening combined with aducanumab resulted in greater amyloid-beta reduction in treated regions than untreated regions over 6 months
Duration of biological effect
24-48 hours
Safety-related matter
No safety or adverse effects are mentioned in the provided text; BBB opening was reversible within 24-48 hours
Brain Region
Ultrasound Parameters
Ultrasound instrument
ExAblate-Neuro-Type2 (Insightec); hemispherical phased-array transducer
FUS Mode
pulsed
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
multiple sessions
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