The antibody aducanumab reduces Abeta plaques in Alzheimer's disease.

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Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A

The antibody aducanumab reduces Abeta plaques in Alzheimer's disease.

Nature. 2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323.

PubMed ID

27582220 [ View in PubMed

]

Abstract

Alzheimer's disease (AD) is characterized by deposition of amyloid-beta (Abeta) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Abeta to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Abeta. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Abeta, and reduce soluble and insoluble Abeta in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Abeta in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating-Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aducanumab	Amyloid beta A4 protein	Protein	Humans	Unknown	Antagonist Binder Antibody	Details