Brain delivery and efficacy of a BBB shuttle-enhanced aducanumab biosimilar in a mouse model of Alzheimer’s disease
Thomas Topilko, Marta Ramos Vega, Franziska Wichern, Allan Jensen, Camilla Stampe Jensen, Jacob Lercke Skytte, Casper Graversen Salinas, Sandra Vergo, Jacob Hecksher-Sørensen, Henrik H. Hansen · FENS Forum 2024
Aβ-directed antibodies with enhanced CNS access have the potential to improve therapeuticoutcomes in Alzheimer's disease (AD). The present study aimed to simultaneously 3D map whole-braindistribution and Aβ plaque clearing efficiency of a blood-brain barrier (BBB) shuttle-enhanced Aβantibody in a transgenic mouse model of AD. 5–9-month-old APP/PS1 transgenic ARTE10 mice (n=8-10 per group) were treated with an aducanumab biosimilar (AduBS, 10 or 50 nmol/kg), aducanumabbiosimilar fused with a mouse transferrin receptor (mTfR) binder as BBB-shuttle (AduBS-BBB, 10nmol/kg) or control hIgG (50 nmol/