Anti-Aβ antibody target engagement: a response to Siemers et al.

Watt, Andrew D; Crespi, Gabriela A. N.; Down, Russell A; Ascher, David B.; Gunn, Adam P; Perez, Keyla; McLean, Catriona; Villemagne, Victor L.; Parker, M.W.; Barnham, Kevin J.; Miles, Luke A.

doi:10.1007/s00401-014-1333-8

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…It is unknown if any of the drugs tested in clinical trial, which target alternative cleavage of APP, or target Aβ species immunologically, have been effective inor isolating the toxic Aβ isoform. Moreover, it was recently shown that not all the therapeutic antibodies bind to Aβ species in plasma or postmortem brain samples, which potentially explains why they were not effective in clinical trial [39].…”

Section: Challenges In Targeting Amyloidmentioning

confidence: 99%

Biometals and Their Therapeutic Implications in Alzheimer's Disease

2015

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No disease modifying therapy exists for Alzheimer's disease (AD). The growing burden of this disease to our society necessitates continued investment in drug development. Over the last decade, multiple phase 3 clinical trials testing drugs that were designed to target established disease mechanisms of AD have all failed to benefit patients. There is, therefore, a need for new treatment strategies. Changes to the transition metals, zinc, copper, and iron, in AD impact on the molecular mechanisms of disease, and targeting these metals might be an alternative approach to treat the disease. Here we review how metals feature in molecular mechanisms of AD, and we describe preclinical and clinical data that demonstrate the potential for metal-based drug therapy.

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Section: Challenges In Targeting Amyloidmentioning

confidence: 99%

Biometals and Their Therapeutic Implications in Alzheimer's Disease

2015

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“…It is no wonder if Watt et al [112] raised "questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventive clinical trials for Alzheimer's disease." When Siemers et al [113] at Lilly argued against these findings, Watt et al [114] defended their findings.…”

Section: Prevention Is the Only Curementioning

confidence: 97%

The amyloid hypothesis is too good to be true

Kurkinen¹

2017

Alzheimers Dement Cogn Neurol

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“…Engineering Abs often requires optimization of not just selectivity and affinity for the given antigen, but also stability, solubility and immunogenicity of the Ab ( 1 ). Optimization of these properties is essential not only for therapeutic use ( 2 , 3 ), but to improve quality and reproducibility in experimental settings ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

mCSM-AB: a web server for predicting antibody–antigen affinity changes upon mutation with graph-based signatures

2016

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Computational methods have traditionally struggled to predict the effect of mutations in antibody–antigen complexes on binding affinity. This has limited their usefulness during antibody engineering and development, and their ability to predict biologically relevant escape mutations. Here we present mCSM-AB, a user-friendly web server for accurately predicting antibody–antigen affinity changes upon mutation which relies on graph-based signatures. We show that mCSM-AB performs better than comparable methods that have been previously used for antibody engineering. mCSM-AB web server is available at http://structure.bioc.cam.ac.uk/mcsm_ab.

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Anti-Aβ antibody target engagement: a response to Siemers et al.

Cited by 5 publications

References 28 publications

Biometals and Their Therapeutic Implications in Alzheimer's Disease

Biometals and Their Therapeutic Implications in Alzheimer's Disease

The amyloid hypothesis is too good to be true

mCSM-AB: a web server for predicting antibody–antigen affinity changes upon mutation with graph-based signatures

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