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

doi:10.1186/s40035-021-00269-8

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

Department of Neurosurgery

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

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.

Original language	English
Article number	44
Journal	Translational Neurodegeneration
Volume	10
Issue number	1
DOIs	https://doi.org/10.1186/s40035-021-00269-8
Publication status	Published - 2021 Dec

Bibliographical note

Funding Information:
This study was supported by a grant from the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Science, ICT, and Future Planning, a Government Department (2016M3C7A1914123). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

Clinical Neurology
Cognitive Neuroscience
Cellular and Molecular Neuroscience

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10.1186/s40035-021-00269-8

Cite this

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title = "Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer{\textquoteright}s disease: a proof-of-concept study",

abstract = "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{\textquoteright}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.",

author = "Park, {So Hee} and Kyoungwon Baik and Seun Jeon and Chang, {Won Seok} and Ye, {Byoung Seok} and Chang, {Jin Woo}",

note = "Funding Information: This study was supported by a grant from the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Science, ICT, and Future Planning, a Government Department (2016M3C7A1914123). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1186/s40035-021-00269-8",

language = "English",

volume = "10",

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T1 - Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease

T2 - a proof-of-concept study

AU - Park, So Hee

AU - Baik, Kyoungwon

AU - Jeon, Seun

AU - Chang, Won Seok

AU - Ye, Byoung Seok

AU - Chang, Jin Woo

N1 - Funding Information: This study was supported by a grant from the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Science, ICT, and Future Planning, a Government Department (2016M3C7A1914123). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - 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.

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

Abstract

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