Quantitative systems pharmacology model for Alzheimer's disease to predict the effect of aducanumab on brain amyloid.
Journal
CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306
Titre abrégé: CPT Pharmacometrics Syst Pharmacol
Pays: United States
ID NLM: 101580011
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
20
12
2021
received:
13
08
2021
accepted:
29
12
2021
pubmed:
15
1
2022
medline:
7
5
2022
entrez:
14
1
2022
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory and cognitive function. Dysregulation of the amyloid-β (Aβ) pathway and amyloid plaque accumulation in the brain are hallmarks of AD. Aducanumab is a human, immunoglobulin gamma 1 monoclonal antibody targeting aggregated forms of Aβ. In phase Ib and phase III studies, aducanumab reduced Aβ plaques in a dose dependent manner, as measured by standard uptake value ratio of amyloid positron emission tomography imaging. The goal of this work was to develop a quantitative systems pharmacology model describing the production, aggregation, clearance, and transport of Aβ as well as the mechanism of action for the drug to understand the relationship between aducanumab dosing regimens and changes of different Aβ species, particularly plaques in the brain. The model was used to better understand the pharmacodynamic effects observed in the clinical trials of aducanumab and assist in the clinical development of future Aβ therapies.
Identifiants
pubmed: 35029320
doi: 10.1002/psp4.12759
pmc: PMC8923729
doi:
Substances chimiques
Amyloid beta-Peptides
0
Antibodies, Monoclonal, Humanized
0
aducanumab
105J35OE21
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
362-372Subventions
Organisme : Biogen
Informations de copyright
© 2022 Biogen. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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