Perspectives on future Alzheimer therapies : amyloid-beta 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...
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Uppsala universitet, Geriatrik
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ftuppsalauniv:oai:DiVA.org:uu-231496 2023-05-15T15:14:33+02:00 Perspectives on future Alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease Lannfelt, Lars Moller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Par 2014 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-231496 https://doi.org/10.1186/alzrt246 eng eng Uppsala universitet, Geriatrik ALZHEIMERS RES THER, 1758-9193, 2014, 6:2, s. 16- http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-231496 doi:10.1186/alzrt246 ISI:000339802800004 info:eu-repo/semantics/openAccess Article, review/survey info:eu-repo/semantics/article text 2014 ftuppsalauniv https://doi.org/10.1186/alzrt246 2023-02-23T21:40:05Z 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-A beta) 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 A beta immunotherapy may have clinically relevant effects. Bapineuzumab (Elan/Pfizer Inc./Johnson & Johnson), a monoclonal antibody targeting fibrillar A beta, was stopped because the desired clinical effect was not seen. Solanezumab (Eli Lilly and Company) was developed to target soluble, monomeric A beta. 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 A beta protofibrils, an A beta 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 A beta protofibrils with high selectivity. It has at least a 1,000-fold higher selectivity for protofibrils as compared with monomers of A beta, 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 ... Article in Journal/Newspaper Arctic Uppsala University: Publications (DiVA) Arctic Alzheimer's Research & Therapy 6 2 16 |
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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-A beta) 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 A beta immunotherapy may have clinically relevant effects. Bapineuzumab (Elan/Pfizer Inc./Johnson & Johnson), a monoclonal antibody targeting fibrillar A beta, was stopped because the desired clinical effect was not seen. Solanezumab (Eli Lilly and Company) was developed to target soluble, monomeric A beta. 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 A beta protofibrils, an A beta 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 A beta protofibrils with high selectivity. It has at least a 1,000-fold higher selectivity for protofibrils as compared with monomers of A beta, 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 ... |
format |
Article in Journal/Newspaper |
author |
Lannfelt, Lars Moller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Par |
spellingShingle |
Lannfelt, Lars Moller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Par Perspectives on future Alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease |
author_facet |
Lannfelt, Lars Moller, Christer Basun, Hans Osswald, Gunilla Sehlin, Dag Satlin, Andrew Logovinsky, Veronika Gellerfors, Par |
author_sort |
Lannfelt, Lars |
title |
Perspectives on future Alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease |
title_short |
Perspectives on future Alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease |
title_full |
Perspectives on future Alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease |
title_fullStr |
Perspectives on future Alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease |
title_full_unstemmed |
Perspectives on future Alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease |
title_sort |
perspectives on future alzheimer therapies : amyloid-beta protofibrils - a new target for immunotherapy with ban2401 in alzheimer's disease |
publisher |
Uppsala universitet, Geriatrik |
publishDate |
2014 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-231496 https://doi.org/10.1186/alzrt246 |
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Arctic |
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Arctic |
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Arctic |
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Arctic |
op_relation |
ALZHEIMERS RES THER, 1758-9193, 2014, 6:2, s. 16- http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-231496 doi:10.1186/alzrt246 ISI:000339802800004 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/alzrt246 |
container_title |
Alzheimer's Research & Therapy |
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6 |
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2 |
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16 |
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1766344997901172736 |