↓ Skip to main content

Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency

Overview of attention for article published in Molecular Neurodegeneration, May 2017
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#2 of 867)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (95th percentile)

Mentioned by

news
53 news outlets
twitter
3 X users
patent
11 patents

Citations

dimensions_citation
39 Dimensions

Readers on

mendeley
83 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency
Published in
Molecular Neurodegeneration, May 2017
DOI 10.1186/s13024-017-0172-1
Pubmed ID
Authors

Michael G. Agadjanyan, Karen Zagorski, Irina Petrushina, Hayk Davtyan, Konstantin Kazarian, Maxim Antonenko, Joy Davis, Charles Bon, Mathew Blurton-Jones, David H. Cribbs, Anahit Ghochikyan

Abstract

The 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-Tau2-18 monoclonal antibodies (mAb) may recognize pathological, but not normal tau at very early stages of tauopathy and prevent or decrease the aggregation of this molecule. Mouse 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). A 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. These findings suggest that Armanezumab could be therapeutic in clinical studies for treatment of AD.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 83 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 16 19%
Student > Bachelor 15 18%
Student > Ph. D. Student 11 13%
Student > Master 7 8%
Student > Doctoral Student 5 6%
Other 11 13%
Unknown 18 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 13%
Agricultural and Biological Sciences 11 13%
Neuroscience 10 12%
Medicine and Dentistry 9 11%
Pharmacology, Toxicology and Pharmaceutical Science 6 7%
Other 14 17%
Unknown 22 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 427. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 May 2023.
All research outputs
#57,453
of 23,394,907 outputs
Outputs from Molecular Neurodegeneration
#2
of 867 outputs
Outputs of similar age
#1,434
of 311,719 outputs
Outputs of similar age from Molecular Neurodegeneration
#1
of 22 outputs
Altmetric has tracked 23,394,907 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 867 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.5. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 311,719 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.