ArticleScientific reports2019
A Rationally Designed Humanized Antibody Selective for Amyloid Beta Oligomers in Alzheimer's Disease.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 74 citations in OpenAlex.
- Characterization of conformation-specific antibodies TOMA-1 and TTCM-1 for recombinant tau monomer and amplified brain derived tau oligomer.Biochimica et biophysica acta. Molecular basis of disease · 2025Article
- Therapeutic Advances in Targeting the Amyloid-β Pathway for Alzheimer's Disease.Brain sciences · 2025Review
- Article
- Nanomaterials in targeting amyloid-β oligomers: current advances and future directions for Alzheimer's disease diagnosis and therapy.Beilstein journal of nanotechnology · 2025Review
- Structures of Oligomeric States of Tau Protein, Amyloid-β, α-Synuclein and Prion Protein Implicated in Alzheimer's Disease, Parkinson's Disease and Prionopathies.International journal of molecular sciences · 2024Review
- A single-domain antibody detects and neutralises toxic AβAlzheimer's research & therapy · 2024Article
- Editorial: Beta-Amyloid oligomer specific treatments for Alzheimer's disease.Frontiers in neuroscience · 2023Article
- Antibody-Mediated Clearance of Brain Amyloid-β: Mechanisms of Action, Effects of Natural and Monoclonal Anti-Aβ Antibodies, and Downstream Effects.Journal of Alzheimer's disease reports · 2023Review
- Aβ42 oligomer-specific antibody ALZ-201 reduces the neurotoxicity of Alzheimer's disease brain extracts.Alzheimer's research & therapy · 2022Article
- Rational Generation of Monoclonal Antibodies Selective for Pathogenic Forms of Alpha-Synuclein.Biomedicines · 2022Article
- Optimizing Epitope Conformational Ensembles Using α-Synuclein Cyclic Peptide "Glycindel" Scaffolds: A Customized Immunogen Method for Generating Oligomer-Selective Antibodies for Parkinson's Disease.ACS chemical neuroscience · 2022Article
- An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- The Interplay of Tau Protein and β-Amyloid: While Tauopathy Spreads More Profoundly Than Amyloidopathy, Both Processes Are Almost Equally Pathogenic.Cellular and molecular neurobiology · 2021Article
- A method for systematically ranking therapeutic drug candidates using multiple uncertain screening criteria.Statistical methods in medical research · 2021Article
- Visualizing and trapping transient oligomers in amyloid assembly pathways.Biophysical chemistry · 2021Review
- The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer's Disease.Frontiers in neuroscience · 2021Article
- Antibody Fragments as Tools for Elucidating Structure-Toxicity Relationships and for Diagnostic/Therapeutic Targeting of Neurotoxic Amyloid Oligomers.International journal of molecular sciences · 2020Review
- Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers.International journal of molecular sciences · 2020Review
- Passive immunotherapies targeting Aβ and tau in Alzheimer's disease.Neurobiology of disease · 2020Review
- Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval.Alzheimer's research & therapy · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Advances in the understanding of Alzheimer's disease (AD) suggest that pathogenesis is not directly related to plaque burden, but rather to soluble toxic amyloid-beta oligomers (AßO). Therapeutic antibodies targeting Aß monomers and/or plaque have shown limited efficacy and dose-limiting adverse events in clinical trials. These findings suggest that antibodies capable of selectively neutralizing toxic AßO may achieve improved efficacy and safety. To this end, we generated monoclonal antibodies against a conformational Aß epitope predicted by computational modeling to be presented on toxic AßO but not monomers or fibrils. The resulting lead antibody, PMN310, showed the desired AßO-selective binding profile. In vitro, PMN310 inhibited AßO propagation and toxicity. In vivo, PMN310 prevented AßO-induced loss of memory formation and reduced synaptic loss and inflammation. A humanized version (huPMN310) compared favorably to other Aß-directed antibodies showing a lack of adverse event-associated binding to Aß deposits in AD brains, and greater selective binding to AßO-enriched AD brain fractions that contain synaptotoxic Aß species. Systemic administration of huPMN310 in mice resulted in brain exposure and kinetics comparable to those of other therapeutic human monoclonal antibodies. Greater selectivity for AßO and the potential to safely administer high doses of huPMN310 are expected to result in enhanced safety and therapeutic potency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.