Affibody-Mediated Sequestration of Amyloid ? Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model.

ABSTRACT: Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid ? (anti-A?) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of A?-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted ZSYM73-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric ZSYM73 affibody for sequestering of monomeric A?-peptides and an ABD for extension of its in vivo half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with ZSYM73-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported in vivo investigation of a systemically delivered scaffold protein against monomeric A?, demonstrating a therapeutic potential for prevention of AD.

SUBMITTER: Boutajangout A 

PROVIDER: S-EPMC6440316 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature