The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

Last Updated on September 9, 2016 by Joseph Gut – thasso

September 09.  2016 – The pre-clinical animal model and Phase 1b placebo-controlled study in prodromal and mild Alzheimer Disease (AD) patients (n=165), both demonstrate that aducanumab reduced amyloid-beta in the brain and the reduction was dose-dependent. Amyloid-beta plaque is associated with the development of AD and it has for a long time been hypothesized that removing it may slow the clinical decline of people who have AD. The newly published study (see below) seems to confirm this in that clinical parameters of decline of brain function have apparently improved in early studies (i.e., clinical Phase Ib) in AD patients. If confirmed in clinical Phase III studies, and if associated clinical safety of aducanumab turns out to be favourable, approval by regulatory authorities is likely, and aducanumab could become an effective therapy option for AD patients.

In the meantime, please see the published study below:

Sevigny J, Chiao P, Bussière 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

Nature 2016;537(7618):50-6

PMID: 27582220

Abstract

Alzheimer’s disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ 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 Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ 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.

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