Jessica Couch

TL;DR: It is shown that bispecific antibodies with optimized binding to the transferrin receptor (TfR) that target β-secretase (BACE1) can cross the BBB and reduce brain amyloid-β (Aβ) in mice.

TL;DR: It is reported that when mice were dosed with therapeutic TfR antibodies, the animals showed acute clinical reactions and a reduction in immature red blood cells, known as reticulocytes, which suggest that the blood-brain barrier is not the only obstacle to surmount on the way to the brain, at least when using TFR as a molecular lift.

TL;DR: It is demonstrated that both human and murine antibodies containing the LALA-PG variant have typical pharmacokinetics in rodents and retain thermostability, enabling efficient knobs-into-holes bispecific antibody production and a robust path to generating highly effector-attenuated bispecial antibodies for preclinical studies.

TL;DR: The authors have identified opportunities to maximize the predictivity of this information to humans while reducing animal use in four key areas; accelerating the uptake of in vitro methods, incorporating the latest science into safety pharmacology assessments, and optimizing rodent study design in biological development.

TL;DR: Alternative approaches, including animal models of disease, genetically modified mice, or use of surrogate molecules, may improve the predictive value of preclinical safety assessments of species-specific biopharmaceuticals, although many caveats associated with these models must be considered.