Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease
The symptomatic drugs currently on the market for Alzheimer’s disease (AD) have no effect on disease progression, and this creates a large unmet medical need. The type of drug that has developed most rapidly in the last decade is immunotherapy: vaccines and, especially, passive vaccination with mono...
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ftpubmed:oai:pubmedcentral.nih.gov:4054967 2023-05-15T15:16:02+02:00 Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease Lannfelt, Lars Möller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Pär 2014-03-24 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054967 http://www.ncbi.nlm.nih.gov/pubmed/25031633 https://doi.org/10.1186/alzrt246 en eng BioMed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC http://www.ncbi.nlm.nih.gov/pubmed/25031633 http://dx.doi.org/10.1186/alzrt246 Copyright © 2014 Lannfelt et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 The licensee has exclusive rights to distribute this article, in any medium, for 12 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. CC-BY Review Text 2014 ftpubmed https://doi.org/10.1186/alzrt246 2015-03-29T00:55:48Z The symptomatic drugs currently on the market for Alzheimer’s disease (AD) have no effect on disease progression, and this creates a large unmet medical need. The type of drug that has developed most rapidly in the last decade is immunotherapy: vaccines and, especially, passive vaccination with monoclonal antibodies. Antibodies are attractive drugs as they can be made highly specific for their target and often with few side effects. Data from recent clinical AD trials indicate that a treatment effect by immunotherapy is possible, providing hope for a new generation of drugs. The first anti-amyloid-beta (anti-Aβ) vaccine developed by Elan, AN1792, was halted in phase 2 because of aseptic meningoencephalitis. However, in a follow-up study, patients with antibody response to the vaccine demonstrated reduced cognitive decline, supporting the hypothesis that Aβ immunotherapy may have clinically relevant effects. Bapineuzumab (Elan/Pfizer Inc./Johnson & Johnson), a monoclonal antibody targeting fibrillar Aβ, was stopped because the desired clinical effect was not seen. Solanezumab (Eli Lilly and Company) was developed to target soluble, monomeric Aβ. In two phase 3 studies, Solanezumab did not meet primary endpoints. When data from the two studies were pooled, a positive pattern emerged, revealing a significant slowing of cognitive decline in the subgroup of mild AD. The Arctic mutation has been shown to specifically increase the formation of soluble Aβ protofibrils, an Aβ species shown to be toxic to neurons and likely to be present in all cases of AD. A monoclonal antibody, mAb158, was developed to target Aβ protofibrils with high selectivity. It has at least a 1,000-fold higher selectivity for protofibrils as compared with monomers of Aβ, thus targeting the toxic species of the peptide. A humanized version of mAb158, BAN2401, has now entered a clinical phase 2b trial in a collaboration between BioArctic Neuroscience and Eisai without the safety concerns seen in previous phase 1 and 2a trials. Experiences from ... Text Arctic PubMed Central (PMC) Arctic Alzheimer's Research & Therapy 6 2 16 |
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Review Lannfelt, Lars Möller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Pär Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease |
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Review |
description |
The symptomatic drugs currently on the market for Alzheimer’s disease (AD) have no effect on disease progression, and this creates a large unmet medical need. The type of drug that has developed most rapidly in the last decade is immunotherapy: vaccines and, especially, passive vaccination with monoclonal antibodies. Antibodies are attractive drugs as they can be made highly specific for their target and often with few side effects. Data from recent clinical AD trials indicate that a treatment effect by immunotherapy is possible, providing hope for a new generation of drugs. The first anti-amyloid-beta (anti-Aβ) vaccine developed by Elan, AN1792, was halted in phase 2 because of aseptic meningoencephalitis. However, in a follow-up study, patients with antibody response to the vaccine demonstrated reduced cognitive decline, supporting the hypothesis that Aβ immunotherapy may have clinically relevant effects. Bapineuzumab (Elan/Pfizer Inc./Johnson & Johnson), a monoclonal antibody targeting fibrillar Aβ, was stopped because the desired clinical effect was not seen. Solanezumab (Eli Lilly and Company) was developed to target soluble, monomeric Aβ. In two phase 3 studies, Solanezumab did not meet primary endpoints. When data from the two studies were pooled, a positive pattern emerged, revealing a significant slowing of cognitive decline in the subgroup of mild AD. The Arctic mutation has been shown to specifically increase the formation of soluble Aβ protofibrils, an Aβ species shown to be toxic to neurons and likely to be present in all cases of AD. A monoclonal antibody, mAb158, was developed to target Aβ protofibrils with high selectivity. It has at least a 1,000-fold higher selectivity for protofibrils as compared with monomers of Aβ, thus targeting the toxic species of the peptide. A humanized version of mAb158, BAN2401, has now entered a clinical phase 2b trial in a collaboration between BioArctic Neuroscience and Eisai without the safety concerns seen in previous phase 1 and 2a trials. Experiences from ... |
format |
Text |
author |
Lannfelt, Lars Möller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Pär |
author_facet |
Lannfelt, Lars Möller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Pär |
author_sort |
Lannfelt, Lars |
title |
Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease |
title_short |
Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease |
title_full |
Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease |
title_fullStr |
Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease |
title_full_unstemmed |
Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease |
title_sort |
perspectives on future alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with ban2401 in alzheimer’s disease |
publisher |
BioMed Central |
publishDate |
2014 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054967 http://www.ncbi.nlm.nih.gov/pubmed/25031633 https://doi.org/10.1186/alzrt246 |
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Arctic |
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Arctic |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC http://www.ncbi.nlm.nih.gov/pubmed/25031633 http://dx.doi.org/10.1186/alzrt246 |
op_rights |
Copyright © 2014 Lannfelt et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 The licensee has exclusive rights to distribute this article, in any medium, for 12 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
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CC-BY |
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https://doi.org/10.1186/alzrt246 |
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Alzheimer's Research & Therapy |
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6 |
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2 |
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16 |
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