A study recently published in the journal Nature indicates that aducanumab shows promise, in both preclinical and clinical settings, in prevention and reduction of amyloid-β (Aβ) plaques in patients with Alzheimer’s.
Aducanumab is a recombinant human monoclonal antibody targeting Aβ aggregates that are believed to play a critical role in the neurodegenerative Alzheimer’s process.
Previous studies using antibody-based immunotherapy against Aβ deposits failed to show promising results. The authors of the Nature study tested the amyloid hypothesis assuming that this previous work had issues with antibodies’ efficacy and specificity.
In this study, Jeff Sevigny and colleagues from Biogen, Cambridge, Massachusetts, USA and Neurimmune, Schlieren-Zurich, Switzerland report that in preclinical settings, in a transgenic mouse model of Alzheimer’s disease, the antibody was able to penetrate the brain, and specifically accumulated and bound to parenchymal, but not vascular Aβ deposits.
In clinical settings, the research team studied the effects of aducanumab in a double blind placebo controlled phase 1b randomized trial. 165 people with early-stage Alzheimer’s disease were given a monthly injection of the antibody for one year, at 33 sites in the US.
The main result from this trial indicates that the treatment with aducanumab contributed to a significant reduction of beta-amyloid plaques in patients with early-stage Alzheimer’s disease, in a time- and dose-dependent way. Moreover, cognitive decline could be significantly slowed in antibody-treated patients as opposed to the placebo group.
As per the mechanism(s) of action of aducanumab, the authors believe that the clearance of amyloid-β deposits was most likely related to the enhanced recruitment of microglia. They argue that an Fc gamma R-mediated microglial recruitment and phagocytosis appeared to contribute to the aducanumab’s effects.
According to telegraph.co.uk, Dr. Roger Nitsch, one of the senior authors of this study, stated that “In the high dose group the amyloid has almost completely disappeared. The effect size of this drug is unprecedented”. Of note, and as per this online article, there are now two large phase-three clinical studies taking place to further evaluate safety and efficacy of aducanumab.
Source: Nature, 2016, 537(7618):50-6. doi: 10.1038/nature19323.
Read more: nature.com
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