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Aβ-Immunotherapeutic strategies: a wide range of approaches for Alzheimer's disease treatment

Published online by Cambridge University Press:  30 June 2016

Laia Montoliu-Gaya  and
Sandra Villegas
Laia Montoliu-Gaya
Affiliation:
Protein Folding and Stability Group, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Facultat de Biociències, 08193 Bellaterra, Barcelona, Spain
Sandra Villegas*
Affiliation:
Protein Folding and Stability Group, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Facultat de Biociències, 08193 Bellaterra, Barcelona, Spain
*
*Corresponding author: Sandra Villegas, Protein Folding and Stability Group, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Facultat de Biociències, 08193 Bellaterra, Barcelona, Spain. E-mail: [email protected]
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Abstract

Current therapies to treat Alzheimer's disease (AD) are focused on ameliorating symptoms instead of treating the underlying causes of AD. The accumulation of amyloid β (Aβ) oligomers, whether by an increase in production or by a decrease in clearance, has been described as the seed that initiates the pathological cascade in AD. Developing therapies to target these species is a vital step in improving AD treatment. Aβ-immunotherapy, especially passive immunotherapy, is a promising approach to reduce the Aβ burden. Up to now, several monoclonal antibodies (mAbs) have been tested in clinical trials on humans, but none of them have passed Phase III. In all likelihood, these trials failed mainly because patients with mild-to-moderate AD were recruited, and thus treatment may have been too late to be effective. Therefore, many ongoing clinical trials are being conducted in patients at the prodromal stage. New structures based on antibody fragments have been engineered intending to improve efficacy and safety. This review presents the properties of this variety of developing treatments and provides a perspective on state-of-the-art of passive Aβ-immunotherapy in AD.

Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 18 , 2016 , e13
Copyright
Copyright © Cambridge University Press 2016 

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