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Sci Transl Med. 2011 May 25;3(84):84ps20. doi: 10.1126/scitranslmed.3002620.

Therapeutic antibodies for brain disorders.

Author information

1
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. smpaulmd@med.cornell.edu

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.

PMID:
21613621
DOI:
10.1126/scitranslmed.3002620
[Indexed for MEDLINE]

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