AUTHOR=Bloomingdale Peter , Bumbaca-Yadav Daniela , Sugam Jonathan , Grauer Steve , Smith Brad , Antonenko Svetlana , Judo Michael , Azadi Glareh , Yee Ka Lai 

TITLE=PBPK-PD modeling for the preclinical development and clinical translation of tau antibodies for Alzheimer’s disease

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.867457

DOI=10.3389/fphar.2022.867457

ISSN=1663-9812

ABSTRACT=Disrupted tau proteostasis and transneuronal spread is a pathological hallmark of Alzheimer’s disease. Neurodegenerative diseases remain an unmet medical need and novel disease modifying therapeutics are paramount. A physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) modeling approach was employed to support the preclinical development and clinical translation of therapeutic antibodies targeting tau for the treatment of Alzheimer’s disease. PBPK-PD modeling enabled a quantitative understanding for the relationship between dose, affinity, and target engagement, which supported lead candidate optimization and predictions of clinically efficacious dosing regimens.