Atwal in Vivo Production β A Therapeutic Antibody Targeting BACE 1 Inhibits Amyloid -

applied to other therapeutic antibodies that require safe passage into the human brain. antibody for treating Alzheimer's disease but also provides a strategy worthy of the ancient Greeks that could be anti-BACE1 antibody. This elegant pair of papers not only demonstrates the therapeutic potential of an anti-BACE1 peptide concentrations in the mouse brain compared to the monospecific β substantially more effective at reducing A BBB and reach therapeutic concentrations in the mouse brain. They then showed that this bispecific antibody was therapeutic promise in their earlier studies. They demonstrated that their bispecific antibody was able to cross the anti-transferrin receptor antibody and the other arm comprising the high-affinity anti-BACE1 antibody that had shown endothelial cell layer. Next, they designed a bispecific mouse antibody with one arm comprising a low-affinity the BBB by receptor-mediated transcytosis and were released into the mouse brain once they got across the So, they made a series of lower-affinity mouse anti-transferrin receptor antibodies and found variants that could cross readily bound to the BBB, it could not detach from the transferrin receptor and hence was not released into the brain. process called receptor-mediated transcytosis. However, when they tested their antibody, they found that although it knew that high-affinity antibodies against the transferrin receptor might be able to cross the BBB using a natural . ). The Genentech researchers et al fellow Genentechie, Mark Dennis, and they devised an ingenious solution (Yu peptide concentrations in the brain sufficiently to obtain a therapeutic effect. So Watts teamed up with β reduce A The researchers knew that they must find a way to increase the amount of antibody getting into the brain to circulation of these animals and to a lesser extent in the brain. peptide in the β antibody into mice and monkeys and demonstrated a sustained decrease in the concentrations of A peptides in cultured primary neurons. Next, Watts and his colleagues injected the β production of aggregation-prone A .). The investigators then showed that this antibody could reduce et al specificity and blocked its activity (Atwal specific anti-BACE1 antibody. So his team engineered an anti-BACE1 antibody that bound to BACE1 with exquisite Watts envisaged that a better approach to blocking BACE1 activity might be passive immunization with a highly side effects. readily cross the BBB because of their small size, they do not show sufficient specificity and hence may have toxic can slowing Alzheimer's disease progression. Although small-molecule inhibitors of BACE1 have been developed and peptides, thus decreasing amyloid plaque formation and β should reduce production of the aggregation-prone A plaques found in the brains of Alzheimer's disease patients. By blocking the activity of BACE1, BACE1 inhibitors ) peptides including those molecular species that aggregate to form the amyloid β (A β precursor protein into amyloid.). BACE1 processes the amyloid et al . and Yu et al boost the amount of this antibody that enters the brain (Atwal -secretase (BACE1), and developing a strategy to β against a popular Alzheimer's disease drug target, the enzyme Enter Ryan Watts and his team at Genentech with their ambitious dual goal of making a therapeutic antibody therapeutic antibodies, limiting their usefulness for treating diseases of the brain and central nervous system. allows only a few select molecules to enter the brain. Unfortunately, this highly effective fortress blocks passage of As impenetrable as the walls of ancient Troy, the tight endothelial cell layer of the blood-brain barrier (BBB) A Trojan Horse Antibody Scales a Mighty Fortress