Treating Alzheimer's disease with monoclonal antibodies: current status and outlook for the future.
In the past decade, Alzheimer's disease drug discovery has been directed at 'disease modifying drugs' that are able to counteract the progression of Alzheimer's disease by intervening in specific parts of its neuropathological process. Passive immunization with monoclonal antibodies (mAbs) may be able to clear toxic amyloid-β species either directly or through microglia or complement activation, thereby halting the amyloid cascade and preventing neurodegeneration and cognitive and functional decline. Thus far, results from two large phase 3 trial programs with bapineuzumab and solaneuzumab, respectively, have brought rather disappointing results. Possible explanations could be that these compounds were either targeting the wrong amyloid-β species, or were given too late in the disease process. Several new mAbs targeting various amyloid-β epitopes are now being tested in ongoing phase 2 and 3 clinical trials. The present review discusses the various mAbs aimed at amyloid-β, summarizes trial results and provides an outlook for the future.
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands ; Alzheimer Research Center, Gebouw Cronenburg, Cronenburg 75, 1081 GM, Amsterdam, The Netherlands.
Niels D
ND
Prins
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
Philip
P
Scheltens