Aducanumab, an antibody developed by the University
of Zurich, has been shown to trigger a meaningful
reduction of harmful beta-amyloid plaques in
patients with early-stage Alzheimer's disease.
These protein deposits in the brain are a classic
sign of Alzheimer's disease and contribute to the
progressive degeneration of brain cells.
The researchers furthermore demonstrated in an early
stage clinical study that, after one year of
treatment with Aducanumab, cognitive decline could
be significantly slowed in antibody-treated patients
as opposed to the placebo group.
Although the causes of Alzheimer's disease are still
unknown, it is clear that the disease commences with
progressive amyloid deposition in the brains of
affected persons between ten and fifteen years
before the emergence of initial clinical symptoms
such as memory loss.
Researchers have now been able to show that
Aducanumab, a human monoclonal antibody, selectively
binds brain amyloid plaques, thus enabling
microglial cells to remove the plaques.
A one-year treatment with the antibody, as part of a
phase Ib study, resulted in almost complete
clearance of the brain amyloid plaques in the study
group patients.
The results, which were realized by researchers at
UZH together with the biotech company “Biogen” and
the UZH spin-off “Neurimmune,” have been published
in the renowned science journal “Nature.”
Reduction of brain amyloid plaque is dependent on
treatment duration and dosage.
“The results of this clinical study make us
optimistic that we can potentially make a great step
forward in treating Alzheimer's disease,” says Roger
M. Nitsch, professor at the Institute for
Regenerative Medicine at UZH. “The effect of the
antibody is very impressive. And the outcome is
dependent on the dosage and length of treatment.”
After one year of treatment, practically no
beta-amyloid plaques could be detected in the
patients who received the highest dose of the
antibody.
The antibody was developed with the help of a
technology platform from “Neurimmune.”
Using blood collected from elderly persons aged up
to one hundred and demonstrating no cognitive
impairment, the researchers isolated precisely those
immune cells whose antibodies are able to identify
toxic beta-amyloid plaques but not the amyloid
precursor protein that is present throughout the
human body and that presumably plays an important
role in the growth of nerve cells.
The good safety profile of Aducanumab in patients
may well be attributed to the antibody’s specific
capacity to bond with the abnormally folded
beta-amyloid protein fragment as well as the fact
that the antibody is of human origin.
Investigational treatment also curbs cognitive
decline.
165 patients with early-stage Alzheimer's disease
were treated in the phase 1b clinical trial.
Although not initially planned as a primary study
objective, the good results encouraged researchers
to additionally investigate how the treatment
affected the symptoms of disease.
This was evaluated via standardized questionnaires
to assess the cognitive abilities and everyday
activities of the patients. “Aducanumab also showed
positive effects on clinical symptoms," is how
Nitsch sums up the findings. “While patients in the
placebo group exhibited significant cognitive
decline, cognitive ability remained distinctly more
stable in patients receiving the antibody.”
Some of the trial participants temporarily suffered
from amyloid-related imaging abnormality (ARIA), an
adverse effect that can be detected via magnetic
resonance imaging. In a minority of cases, this was
accompanied by temporary mild to moderate headaches.
The UZH researchers believe that ARIA is a
measurable biological effect of amyloid clearance.
The promising effects of Aducanumab are currently
being investigated in two large phase three clinical
studies to further evaluate safety and efficacy.
Involving over 300 centers in 20 countries
throughout North America, Europe, and Asia, these
studies are evaluating the effectiveness and safety
of the antibody on a total of 2,700 patients with
early-stage Alzheimer's disease.
For more information
Jeff Sevigny, Ping Chiao, Thierry Bussière, Paul H.
Weinreb, Leslie Williams, Marcel Maier, Robert
Dunstan, Stephen Salloway, Tianle Chen, Yan Ling,
John O’Gorman, Fang Qian, Mahin Arastu, Mingwei Li,
Sowmya Chollate, Melanie S. Brennan, Omar Quintero-Monzon,
Robert H. Scannevin, H. Moore Arnold, Thomas Engber,
Kenneth Rhodes, James Ferrero, Yaming Hang, Alvydas
Mikulskis, Jan Grimm, Christoph Hock, Roger M.
Nitsch & Alfred Sandrock.
The antibody aducanumab reduces Aß plaques in
Alzheimer’s disease. Nature. September 1, 2016.
doi:10.1038/nature19323
Link...
Institute of Regenerative Medicine
University of Zurich
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