Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody.

ABSTRACT:

Background

Transferrin receptor 1 (TfR1) mediated brain delivery of antibodies could become important for increasing the efficacy of emerging immunotherapies in Alzheimer's disease (AD). However, age, dose, binding to TfR1 on blood cells, and pathology could influence the TfR1-mediated transcytosis of TfR1-binders across the blood-brain barrier (BBB). The aim of the study was, therefore, to investigate the impact of these factors on the brain delivery of a bispecific TfR1-transported Aβ-antibody, mAb3D6-scFv8D3, in comparison with the conventional antibody mAb3D6.

Methods

Young (3-5 months) and aged (17-20 months) WT and tg-ArcSwe mice (AD model) were injected with ¹²⁵I-labeled mAb3D6-scFv8D3 or mAb3D6. Three different doses were used in the study, 0.05 mg/kg (low

SUBMITTER: Faresjo R 

PROVIDER: S-EPMC10173660 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature