Cargando…
Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound
The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer’s disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196825/ https://www.ncbi.nlm.nih.gov/pubmed/32284421 http://dx.doi.org/10.1073/pnas.2002571117 |
_version_ | 1783528778896506880 |
---|---|
author | Rezai, Ali R. Ranjan, Manish D’Haese, Pierre-François Haut, Marc W. Carpenter, Jeffrey Najib, Umer Mehta, Rashi I. Chazen, J. Levi Zibly, Zion Yates, Jennifer R. Hodder, Sally L. Kaplitt, Michael |
author_facet | Rezai, Ali R. Ranjan, Manish D’Haese, Pierre-François Haut, Marc W. Carpenter, Jeffrey Najib, Umer Mehta, Rashi I. Chazen, J. Levi Zibly, Zion Yates, Jennifer R. Hodder, Sally L. Kaplitt, Michael |
author_sort | Rezai, Ali R. |
collection | PubMed |
description | The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer’s disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions. |
format | Online Article Text |
id | pubmed-7196825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-71968252020-05-06 Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound Rezai, Ali R. Ranjan, Manish D’Haese, Pierre-François Haut, Marc W. Carpenter, Jeffrey Najib, Umer Mehta, Rashi I. Chazen, J. Levi Zibly, Zion Yates, Jennifer R. Hodder, Sally L. Kaplitt, Michael Proc Natl Acad Sci U S A Biological Sciences The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer’s disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions. National Academy of Sciences 2020-04-28 2020-04-13 /pmc/articles/PMC7196825/ /pubmed/32284421 http://dx.doi.org/10.1073/pnas.2002571117 Text en Copyright © 2020 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Rezai, Ali R. Ranjan, Manish D’Haese, Pierre-François Haut, Marc W. Carpenter, Jeffrey Najib, Umer Mehta, Rashi I. Chazen, J. Levi Zibly, Zion Yates, Jennifer R. Hodder, Sally L. Kaplitt, Michael Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound |
title | Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound |
title_full | Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound |
title_fullStr | Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound |
title_full_unstemmed | Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound |
title_short | Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound |
title_sort | noninvasive hippocampal blood−brain barrier opening in alzheimer’s disease with focused ultrasound |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196825/ https://www.ncbi.nlm.nih.gov/pubmed/32284421 http://dx.doi.org/10.1073/pnas.2002571117 |
work_keys_str_mv | AT rezaialir noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT ranjanmanish noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT dhaesepierrefrancois noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT hautmarcw noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT carpenterjeffrey noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT najibumer noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT mehtarashii noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT chazenjlevi noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT ziblyzion noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT yatesjenniferr noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT hoddersallyl noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound AT kaplittmichael noninvasivehippocampalbloodbrainbarrieropeninginalzheimersdiseasewithfocusedultrasound |