Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’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, fea...

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Autores principales:	So Hee Park, Kyoungwon Baik, Seun Jeon, Won Seok Chang, Byoung Seok Ye, Jin Woo Chang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Alzheimer disease Focused ultrasound Blood–brain barrier Amyloid beta-peptides Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/f18ef97d94344d85a042423ae5670bea
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spelling	oai:doaj.org-article:f18ef97d94344d85a042423ae5670bea2021-11-08T11:03:23ZExtensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study10.1186/s40035-021-00269-82047-9158https://doaj.org/article/f18ef97d94344d85a042423ae5670bea2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40035-021-00269-8https://doaj.org/toc/2047-9158Abstract 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.So Hee ParkKyoungwon BaikSeun JeonWon Seok ChangByoung Seok YeJin Woo ChangBMCarticleAlzheimer diseaseFocused ultrasoundBlood–brain barrierAmyloid beta-peptidesNeurology. Diseases of the nervous systemRC346-429ENTranslational Neurodegeneration, Vol 10, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer disease Focused ultrasound Blood–brain barrier Amyloid beta-peptides Neurology. Diseases of the nervous system RC346-429
spellingShingle	Alzheimer disease Focused ultrasound Blood–brain barrier Amyloid beta-peptides Neurology. Diseases of the nervous system RC346-429 So Hee Park Kyoungwon Baik Seun Jeon Won Seok Chang Byoung Seok Ye Jin Woo Chang Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study
description	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.
format	article
author	So Hee Park Kyoungwon Baik Seun Jeon Won Seok Chang Byoung Seok Ye Jin Woo Chang
author_facet	So Hee Park Kyoungwon Baik Seun Jeon Won Seok Chang Byoung Seok Ye Jin Woo Chang
author_sort	So Hee Park
title	Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study
title_short	Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study
title_full	Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study
title_fullStr	Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study
title_full_unstemmed	Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study
title_sort	extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of alzheimer’s disease: a proof-of-concept study
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f18ef97d94344d85a042423ae5670bea
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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

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