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Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease
Immunotherapy against amyloid-beta (Aβ) is a promising option for the treatment of Alzheimer’s disease (AD). Aβ exists as various species, including monomers, oligomers, protofibrils, and insoluble fibrils in plaques. Oligomers and protofibrils have been shown to be toxic, and removal of these aggre...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119362/ https://www.ncbi.nlm.nih.gov/pubmed/36253511 http://dx.doi.org/10.1007/s13311-022-01308-6 |
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author | Söderberg, Linda Johannesson, Malin Nygren, Patrik Laudon, Hanna Eriksson, Fredrik Osswald, Gunilla Möller, Christer Lannfelt, Lars |
author_facet | Söderberg, Linda Johannesson, Malin Nygren, Patrik Laudon, Hanna Eriksson, Fredrik Osswald, Gunilla Möller, Christer Lannfelt, Lars |
author_sort | Söderberg, Linda |
collection | PubMed |
description | Immunotherapy against amyloid-beta (Aβ) is a promising option for the treatment of Alzheimer’s disease (AD). Aβ exists as various species, including monomers, oligomers, protofibrils, and insoluble fibrils in plaques. Oligomers and protofibrils have been shown to be toxic, and removal of these aggregates might represent an effective treatment for AD. We have characterized the binding properties of lecanemab, aducanumab, and gantenerumab to different Aβ species with inhibition ELISA, immunodepletion, and surface plasmon resonance. All three antibodies bound monomers with low affinity. However, lecanemab and aducanumab had very weak binding to monomers, and gantenerumab somewhat stronger binding. Lecanemab was distinctive as it had tenfold stronger binding to protofibrils compared to fibrils. Aducanumab and gantenerumab preferred binding to fibrils over protofibrils. Our results show different binding profiles of lecanemab, aducanumab, and gantenerumab that may explain clinical results observed for these antibodies regarding both efficacy and side effects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01308-6. |
format | Online Article Text |
id | pubmed-10119362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-101193622023-04-22 Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease Söderberg, Linda Johannesson, Malin Nygren, Patrik Laudon, Hanna Eriksson, Fredrik Osswald, Gunilla Möller, Christer Lannfelt, Lars Neurotherapeutics Original Article Immunotherapy against amyloid-beta (Aβ) is a promising option for the treatment of Alzheimer’s disease (AD). Aβ exists as various species, including monomers, oligomers, protofibrils, and insoluble fibrils in plaques. Oligomers and protofibrils have been shown to be toxic, and removal of these aggregates might represent an effective treatment for AD. We have characterized the binding properties of lecanemab, aducanumab, and gantenerumab to different Aβ species with inhibition ELISA, immunodepletion, and surface plasmon resonance. All three antibodies bound monomers with low affinity. However, lecanemab and aducanumab had very weak binding to monomers, and gantenerumab somewhat stronger binding. Lecanemab was distinctive as it had tenfold stronger binding to protofibrils compared to fibrils. Aducanumab and gantenerumab preferred binding to fibrils over protofibrils. Our results show different binding profiles of lecanemab, aducanumab, and gantenerumab that may explain clinical results observed for these antibodies regarding both efficacy and side effects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01308-6. Springer International Publishing 2022-10-17 2023-01 /pmc/articles/PMC10119362/ /pubmed/36253511 http://dx.doi.org/10.1007/s13311-022-01308-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Söderberg, Linda Johannesson, Malin Nygren, Patrik Laudon, Hanna Eriksson, Fredrik Osswald, Gunilla Möller, Christer Lannfelt, Lars Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease |
title | Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease |
title_full | Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease |
title_fullStr | Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease |
title_full_unstemmed | Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease |
title_short | Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease |
title_sort | lecanemab, aducanumab, and gantenerumab — binding profiles to different forms of amyloid-beta might explain efficacy and side effects in clinical trials for alzheimer’s disease |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119362/ https://www.ncbi.nlm.nih.gov/pubmed/36253511 http://dx.doi.org/10.1007/s13311-022-01308-6 |
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