Translational minimal physiologically based pharmacokinetic model for transferrin receptor-mediated brain delivery of antibodies.

ABSTRACT: Successful development of monoclonal antibodies (mAbs) for the treatment of central nervous system disorders has been challenging due to their minimal ability to cross the blood-brain barrier (BBB), resulting in poor brain exposure. Bispecific antibodies (bsAb) that bind to transmembrane protein expressed at the BBB, such as the transferrin receptor (TfR), have shown enhanced brain exposure in rodents and non-human primate (NHP) due to receptor-mediated transcytosis. However, it remains unclear how preclinical findings translate to humans. Moreover, optimal TfR binding affinity remains a subject of debate. Model-informed drug discovery and development is a powerful approach that has been successfully used to support research and development. The goal of this analysis was to expand a publis

SUBMITTER: Muliaditan M 

PROVIDER: S-EPMC12203839 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature