Article

Therapeutic antibodies for brain disorders.

Helen and Robert Appel Alzheimer's Disease Research Institute, Department of Neurology and Neuroscience, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
Science translational medicine (Impact Factor: 14.41). 05/2011; 3(84):84ps20. DOI: 10.1126/scitranslmed.3002620
Source: PubMed

ABSTRACT The enzyme β-secretase (BACE1) remains an important potential disease-modifying target for developing drugs to treat Alzheimer's disease. However, finding selective BACE1 inhibitors that can penetrate the brain has proved challenging. In this issue of Science Translational Medicine, a pair of studies describes a new approach to inhibiting BACE1 using a human monoclonal antibody that uses receptor-mediated transcytosis to cross the blood brain barrier (Atwal et al. and Yu et al.). The authors engineer a low-affinity bispecific monoclonal antibody targeting both BACE1 and the transferrin receptor and show that this antibody enters the brain more readily and inhibits BACE1 activity more efficiently than does a monospecific antibody against BACE1 alone. These findings should stimulate attempts to use receptor-mediated transcytosis to increase brain uptake of therapeutic antibodies for a variety of brain disorders.

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