ArticleFrontiers in pharmacology2022
PBPK-PD modeling for the preclinical development and clinical translation of tau antibodies for Alzheimer's disease.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Integrating In-vitro Permeability Assays within PBPK Modeling to Predict CNS Distribution of Standard and Engineered Antibodies.The AAPS journal · 2026Article
- Model-Based Design of Sustained-Release Formulations of Anti-TNF-α Monoclonal Antibodies for Intravitreal Administration.Pharmaceutics · 2026Article
- Mechanistic modeling of amyloid dynamics relating to Alzheimer's disease progression.Frontiers in aging neuroscience · 2026Article
- Practical Pharmacokinetic-Pharmacodynamic Models in Oncology.Pharmaceutics · 2025Review
- Modernizing Preclinical Drug Development: The Role of New Approach Methodologies.ACS pharmacology & translational science · 2025Review
- Synaptotoxic effects of extracellular tau are mediated by its microtubule-binding region.Acta neuropathologica · 2025Article
- Development of an mPBPK machine learning framework for early target pharmacology assessment of biotherapeutics.Scientific reports · 2025Article
- Targeted drug delivery in neurodegenerative diseases: the role of nanotechnology.Frontiers in medicine · 2025Review
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Computational neurosciences and quantitative systems pharmacology: a powerful combination for supporting drug development in neurodegenerative diseases.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Investigation of Antibody Pharmacokinetics in the Brain Following Intra-CNS Administration and Development of PBPK Model to Characterize the Data.The AAPS journal · 2024Article
- Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model.Scientific reports · 2023Article
- Editorial: Model-informed decision making in the preclinical stages of pharmaceutical research and development.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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. Our objective was to develop a mechanistic mathematical model to enhance our understanding of tau antibody pharmacokinetics and pharmacodynamics in animals and humans. 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. The pharmacokinetics of a tau antibody was evaluated in rat and non-human primate microdialysis studies. Model validation for humans was performed using publicly available clinical data for gosuranemab. In-silico analyses were performed to predict tau engagement in human brain for a range of tau antibody affinities and various dosing regimens. 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.
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