Efficacy of antibody-based therapies to treat Alzheimer's disease: Just a matter of timing?

摘要

A pharmaceutical intervention that has received great attention in recent years for treating Alzheimer's disease (AD) is the use of antibodies targeting amyloid beta (Abeta) in the brain, as the formation of Abeta plaques is considered as being the driving force for the development and progression of AD. Recently, a Phase III trial in patients with mild-to-moderate AD has provided ambivalent evidence for the efficacy of this intervention. In this trial, the intravenous administration of bapineuzumab, a monoclonal antibody targeting Abeta in the brain, for 78 weeks led to a reduction of cerebrospinal fluid levels of phosphorylated tau and evidence for lower Abeta accumulation in the brain of AD patients who carried APOE e4. However, this treatment did not improve clinical outcomes (e.g. the rate of cognitive decline) in these patients. Similar null results with respect to the rate of cognitive decline were found in a separate Phase III clinical trial after treatment with solanezumab.