Therapeutic antibodies for brain disorders.

TitleTherapeutic antibodies for brain disorders.
Publication TypeJournal Article
Year of Publication2011
AuthorsPaul SM
JournalSci Transl Med
Date Published2011 May 25
KeywordsAlzheimer Disease, Amyloid Precursor Protein Secretases, Antibodies, Aspartic Acid Endopeptidases, Brain, Brain Diseases, Humans

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.

Alternate JournalSci Transl Med
PubMed ID21613621