The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Nature,
v.537 no.7618 = no.7618,
2016년, pp.50 - 56
Sevigny, Jeff
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Chiao, Ping
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Bussière, Thierry
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Weinreb, Paul H.
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Williams, Leslie
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Maier, Marcel
(Neurimmune, Schlieren-Zurich 8952, Switzerland)
,
Dunstan, Robert
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Salloway, Stephen
(Butler Hospital, Providence, Rhode Island 02906, USA)
,
Chen, Tianle
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Ling, Yan
(Biogen, Cambridge, Massachusetts 02142, USA)
,
O’Gorman, John
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Qian, Fang
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Arastu, Mahin
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Li, Mingwei
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Chollate, Sowmya
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Brennan, Melanie S.
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Quintero-Monzon, Omar
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Scannevin, Robert H.
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Arnold, H. Moore
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Engber, Thomas
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Rhodes, Kenneth
(Biogen, Cambridge, Massachusetts 02142, USA)
,
Ferrero, James
(Biogen, Cambridge, Mas)
,
Hang, Yaming
,
Mikulskis, Alvydas
,
Grimm, Jan
,
Hock, Christoph
,
Nitsch, Roger M.
,
Sandrock, Alfred
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 h...
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.
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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