Data_Sheet_2_Affibody-Mediated Sequestration of Amyloid β Demonstrates Preventive Efficacy in a Transgenic Alzheimer’s Disease Mouse Model.PDF (217.36 kB)

Data_Sheet_2_Affibody-Mediated Sequestration of Amyloid β Demonstrates Preventive Efficacy in a Transgenic Alzheimer’s Disease Mouse Model.PDF

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posted on 22.03.2019, 13:29 by Allal Boutajangout, Hanna Lindberg, Abdulaziz Awwad, Arun Paul, Rabaa Baitalmal, Ismail Almokyad, Ingmarie Höidén-Guthenberg, Elin Gunneriusson, Fredrik Y. Frejd, Torleif Härd, John Löfblom, Stefan Ståhl, Thomas Wisniewski

Different strategies for treatment and prevention of Alzheimer’s disease (AD) are currently under investigation, including passive immunization with anti-amyloid β (anti-Aβ) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of Aβ-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 Aβ-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 Aβ, demonstrating a therapeutic potential for prevention of AD.

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