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Extensive frontal focused ultrasound mediated blood-brain barrier opening for the treatment of Alzheimer's disease: a proof-of-concept study

 So Hee Park  ;  Kyoungwon Baik  ;  Seun Jeon  ;  Won Seok Chang  ;  Byoung Seok Ye  ;  Jin Woo Chang 
Journal Title
Issue Date
Alzheimer disease ; Amyloid beta-peptides ; Blood–brain barrier ; Focused ultrasound
Background: Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening has shown efficacy in removal of amyloid plaque and improvement of cognitive functions in preclinical studies, but this is rarely reported in clinical studies. This study was conducted to evaluate the safety, feasibility and potential benefits of repeated extensive BBB opening.

Methods: In this open-label, prospective study, six patients with Alzheimer's disease (AD) were enrolled at Severance Hospital in Korea between August 2020 and September 2020. Five of them completed the study. FUS-mediated BBB opening, targeting the bilateral frontal lobe regions over 20 cm3, was performed twice at three-month intervals. Magnetic resonance imaging, 18F-Florbetaben (FBB) positron emission tomography, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) and comprehensive neuropsychological tests were performed before and after the procedures.

Results: FUS targeted a mean volume of 21.1 ± 2.7 cm3 and BBB opening was confirmed at 95.7% ± 9.4% of the targeted volume. The frontal-to-other cortical region FBB standardized uptake value ratio at 3 months after the procedure showed a slight decrease, which was statistically significant, compared to the pre-procedure value (- 1.6%, 0.986 vs1.002, P = 0.043). The CGA-NPI score at 2 weeks after the second procedure significantly decreased compared to baseline (2.2 ± 3.0 vs 8.6 ± 6.0, P = 0.042), but recovered after 3 months (5.2 ± 5.8 vs 8.6 ± 6.0, P = 0.89). No adverse effects were observed.

Conclusions: The repeated and extensive BBB opening in the frontal lobe is safe and feasible for patients with AD. In addition, the BBB opening is potentially beneficial for amyloid removal in AD patients.
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Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Park, So Hee(박소희)
Baik, Kyoungwon(백경원) ORCID logo https://orcid.org/0000-0001-7215-375X
Ye, Byoung Seok(예병석) ORCID logo https://orcid.org/0000-0003-0187-8440
Chang, Won Seok(장원석) ORCID logo https://orcid.org/0000-0003-3145-4016
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
Jeon, Seun(전세운)
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