ArticleMolecular neurodegeneration2017
Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 57 citations in OpenAlex.
- Active Vaccination Strategies for Alzheimer's Disease: An Expanded Review.European journal of immunology · 2026Review
- Tau-targeting active immunotherapy slows progression and reduces pathology in mouse models of tauopathy.Brain pathology (Zurich, Switzerland) · 2026Article
- N-terminally acetylated Met11-Tau: a new pathological truncated Tau species with functional relevance in Alzheimer's disease.Translational neurodegeneration · 2026Article
- Timing matters: early administration of a high-affinity antibody targeting the tau repeat domain prevents aggregation in a mouse tauopathy model.Alzheimer's research & therapy · 2026Article
- Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.Acta neuropathologica communications · 2025Article
- Review
- Implications of Tau Dysregulation in Huntington's Disease and Potential for New Therapeutics.Journal of Huntington's disease · 2023Review
- Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates.NPJ vaccines · 2022Article
- Tau Toxicity in Neurodegeneration.Molecular neurobiology · 2022Review
- Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies.NPJ vaccines · 2022Article
- Review
- Novel Therapies for Parkinsonian Syndromes-Recent Progress and Future Perspectives.Frontiers in molecular neuroscience · 2021Review
- Conformation-selective tau monoclonal antibodies inhibit tau pathology in primary neurons and a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2020Article
- Asparagine residue 368 is involved in Alzheimer's disease tau strain-specific aggregation.The Journal of biological chemistry · 2020Article
- Recent advances in tau-directed immunotherapy against Alzheimer's disease: an overview of pre-clinical and clinical development.Metabolic brain disease · 2020Review
- Tau immunotherapies: Lessons learned, current status and future considerations.Neuropharmacology · 2020Review
- Active immunization with tau epitope in a mouse model of tauopathy induced strong antibody response together with improvement in short memory and pSer396-tau pathology.Neurobiology of disease · 2020Article
- Passive immunotherapy for N-truncated tau ameliorates the cognitive deficits in two mouse Alzheimer's disease models.Brain communications · 2020Article
- Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.Alzheimer's research & therapy · 2019Article
- A MultiTEP platform-based epitope vaccine targeting the phosphatase activating domain (PAD) of tau: therapeutic efficacy in PS19 mice.Scientific reports · 2019Article
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11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD, whereas at the late stages promoting the clearing of Aβ alone may be insufficient to halt the disease progression. At the same time, pathological tau correlates much better with the degree of dementia than Aβ deposition. Therefore, targeting pathological tau may provide a more promising approach for the treatment of advanced stages of AD. Recent data demonstrates that the N-terminal region of tau spanning aa 2-18 termed "phosphatase activation domain" that is normally hidden in the native protein in 'paperclip'-like conformation, becomes exposed in pathological tau and plays an essential role in the inhibition of fast axonal transport and in aggregation of tau. Hence, we hypothesized that anti-Tau
methodsMouse mAbs were generated using standard hybridoma methodology. CDR grafting was used for humanization of mouse mAb. Humanized mAb (Armanezumab) was characterized and tested in vitro/ex vivo/in vivo using biochemical and immunological methods (HPLC, Biacore, ELISA, IHC, FRET, etc.). Stable DG44 cell line expressing Armanezumab was generated by clone selection with increased concentrations of methotrexate (MTX).
resultsA panel of mouse mAbs was generated, clone 1C9 was selected based on binding to pathological human tau with high affinity and humanized. Fine epitope mapping revealed conservation of the epitope of human tau recognized by the parent murine mAb and Armanezumab. Importantly, Armanezumab (i) bound to tau with high affinity as determined by Biacore; (ii) bound pathological tau in brains from AD, FTD and Pick's disease cases; (iii) inhibited seeding effect of aggregated tau from brain lysate of P301S Tg mice; (iv) inhibited cytotoxic effect of tau oligomers; (v) reduced total tau (HT7) and AT100, PHF1, AT8, AT180, p212, p214-positive tau species in brains of tau transgenic mice after intracranial injection. A stable CHO cell line producing >1.5 g/l humanized mAb, Armanezumab was generated.
conclusionThese findings suggest that Armanezumab could be therapeutic in clinical studies for treatment of AD.
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