25 May 2011
Vol 3, Issue 84

About The Cover

Cover image expansion

ONLINE COVER Crossing the Rubicon. A major problem with treating diseases of the central nervous system is to get drugs across the blood-brain barrier and into the brain. This is a tough problem for very large molecules like antibodies. Now Atwal et al. and Yu et al. have developed a designer antibody (yellow and green) that is able to cross the blood-brain barrier and block a brain enzyme called BACE1 (clear semicircle) that has been implicated in Alzheimer's disease. One arm of this bispecific designer antibody binds with low affinity to the transferrin receptor expressed by endothelial cells that comprise the blood-brain barrier enabling the antibody to leave the circulation (red) and enter the brain. The other arm of the antibody binds with high affinity to BACE1 expressed by neurons (beige), blocking the activity of this enzyme and preventing buildup of the toxic amyloid-β peptides that kill neurons. This bispecific designer antibody strategy may be useful for developing therapeutic antibodies for treating not only Alzheimer's disease but also other diseases of the central nervous system. [CREDIT: A. BRUCE]