Novel Human Monoclonal Antibody Shows Promise for Treating Alzheimer's Disease

A human monoclonal antibody that targets aggregated forms of amyloid-beta (Abeta) protein was shown in a phase Ib clinical study to reduce amyloid plaques in patients with early Alzheimer's disease and to slow or prevent cognitive decline in these individuals.

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.

In a new approach, investigators at the University of Zurich (Switzerland) in collaboration with colleagues at the biotech companies Biogen (Cambridge, MA, USA) and Neurimmune (Schlieren, Switzerland) have used the novel human monoclonal antibody aducanumab to treat AD.

Aducanumab was isolated initially from immune cells obtained from elderly individuals whose antibodies were able to identify toxic beta-amyloid plaques but not amyloid precursor protein. In a transgenic mouse model of AD, aducanumab was shown to enter the brain, bind parenchymal Abeta, and reduce soluble and insoluble Abeta in a dose-dependent manner.

A group of 165 patients with early-stage Alzheimer's disease were treated for one year with aducanumab in a phase 1b clinical trial. Results of the trial published in the August 31, 2016, online edition of the journal Nature revealed that aducanumab reduced brain Abeta in a dose- and time-dependent manner with only minimal adverse side effects. Treatment was accompanied by a slowing of cognitive decline.

"The results of this clinical study make us optimistic that we can potentially make a great step forward in treating Alzheimer's disease," said contributing author Dr. Roger M. Nitsch, professor of medicine at the University of Zurich. "The effect of the antibody is very impressive. And the outcome is dependent on the dosage and length of treatment. Aducanumab also showed positive effects on clinical symptoms. While patients in the placebo group exhibited significant cognitive decline, cognitive ability remained distinctly more stable in patients receiving the antibody."

Evaluation of aducanumab will continue in two large phase three clinical studies that will further examine its safety and efficacy for treating AD. These studies involve more than 2,700 patients in 300 centers in 20 countries throughout North America, Europe, and Asia.

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University of Zurich
Biogen
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