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  • [Nature.] The antibody aducanumab reduces Aβ plaques in Alzheimer's disease.

    Biogen / Alfred Sandrock*

  • 출처
    Nature.
  • 등재일
    2016 Aug 31
  • 저널이슈번호
    537(7618):50-6. doi: 10.1038/nature19323.
  • 내용

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    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.

     

    Author information

    Sevigny J1, Chiao P1, Bussière T1, Weinreb PH1, Williams L1, Maier M2, Dunstan R1, Salloway S3, Chen T1, Ling Y1, O'Gorman J1, Qian F1, Arastu M1, Li M1, Chollate S1, Brennan MS1, Quintero-Monzon O1, Scannevin RH1, Arnold HM1, Engber T1, Rhodes K1, Ferrero J1, Hang Y1, Mikulskis A1, Grimm J2, Hock C2,4, Nitsch RM2,4, Sandrock A1.

    1Biogen, Cambridge, Massachusetts 02142, USA.

    2Neurimmune, Schlieren-Zurich 8952, Switzerland.

    3Butler Hospital, Providence, Rhode Island 02906, USA.

    4Institute for Regenerative Medicine, University of Zurich, Zurich 8952, Switzerland. 

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