Figure 6.

Model of transport of HIRMAb-IDUA fusion protein from the blood to the brain ECS across the capillary endothelium. The model includes rate constants of HIRMAb-IDUA dissociation from (k₂, k₄) and association with (k₁, k₅) the IR; rate constant for endocytosis (k₃) of the complex of the IR and HIRMAb-IDUA into the intra-endothelial compartment; rate constant for HIRMAb-IDUA exocytosis (k₇) into the brain ECS; the rate constant (k₆) for IR recycling back to the luminal endothelial membrane; and the rate constant (k₀) for cerebral plasma flow. The model includes rate constants for HIRMAb-IDUA removal from plasma (μ_B) via erythrocyte binding, removal from the intra-endothelial compartment (μ_E) via a mechanism other than exocytosis, and removal from the brain ECS (μ_F) via either degradation or efflux back to the blood. Adapted from [35], Copyright© 2021 licensed under Creative Commons Attribution License (CC-BY). Image created with Biorender.com.