Release Date: 08/31/2016
A clinical trial studying a novel antibody therapy for Alzheimer’s disease (AD), called aducanumab, has demonstrated the ability to reduce amyloid plaque in the brain and slow cognitive decline. These study results, authored by researchers at Butler Hospital and Brown University in Providence, R.I.; Biogen, in Cambridge, Mass.; and Neurimmune, and the University of Zurich, in Switzerland; are published in the September 1, 2016 issue of Nature.
“Reducing amyloid plaque, a primary marker of Alzheimer’s disease, provides promising new direction in our search for preventions and treatments of Alzheimer’s disease and moves us closer to meeting the US National Plan to find treatment breakthroughs by 2025,” said study author Stephen Salloway, MD, director of the Memory and Aging Program at Butler Hospital, professor of Neurology and Psychiatry at The Alpert Medical School of Brown University. The Memory and Aging Program at Butler Hospital was a leading clinical trial site for Phase 1b study, and is currently enrolling participants in the Phase III trial.
Amyloid plaque is thought to be a primary cause of the synaptic dysfunction and neurodegeneration that underlies the characteristic progression of AD. Previous attempts to specifically target amyloid plaque therapeutically have failed to meet their primary outcomes. In the paper, study authors describe the development of aducanumab, a unique human monoclonal antibody, and how it selectively targets amyloid beta protein.
Utilizing the novel therapy, researchers conducted a double-blind, placebo-controlled Phase Ib randomized trial to evaluate the safety and tolerability of monthly aducanumab injections in patients with mild cognitive impairment or mild dementia due to AD. A group of 165 study participants received monthly infusions of a placebo, or one, three, six, or ten milligrams per kilogram doses of aducanumab for one year. Changes in the amount of amyloid plaque in the brains of participants were measured using molecular positron emission tomography (PET) imaging at 24 and 54 weeks of infusions. After 54 weeks, amyloid plaque was significantly reduced in the brains of patients who received aducanumab. Higher doses of aducanumab were associated with greater amyloid reduction, while there was little change in the brains of those who received the placebo.
Higher aducanumab doses and greater amyloid plaque reductions were also associated with slower cognitive decline in study participants. However, researchers note that this study was not designed to definitively address the antibody’s impact on cognitive decline and the clinical effects of the antibody need to be confirmed in larger studies. Of the 40 study participants that discontinued treatment in the trial, 20 did so due to adverse effects, which included dose-dependent amyloid related imaging abnormalities (ARIA). Characterized as fluid in the brain due to the breakup of amyloid plaque, ARIA is detected via magnetic resonance imaging (MRI), and upon detection, treatment doses may be halted until symptoms dissipate. In this phase of the clinical trial, researchers learned that participants with the ApoE 4 gene were more likely to develop ARIA with higher doses of aducanumab. With this new information, the maximum dose for participants with this gene has been lowered for the next phase of the trial.
The next stage of research includes two Phase III clinical trials involving a larger number of participants, and testing aducanumab’s efficacy and safety, and whether the trial results can be duplicated, confirming if the drug does reduce amyloid plaque in the brain and slow the progression of cognitive decline. “We are excited to be a global leader in the Phase III program,” said Dr. Stephen Salloway. “As the frontline connection to the patients and families, we are proud to be a part of research bringing new hope to those most affected by this disease.”
About Butler Hospital
Butler Hospital, a member of Care New England, is the only private, nonprofit psychiatric and substance abuse hospital serving adults, seniors and adolescents in Rhode Island and southeastern New England. Founded in 1844, it was the first hospital in Rhode Island and has earned a reputation as the leading provider of innovative psychiatric treatments in the region. The Major Affiliated Teaching Hospital for Psychiatry and Behavioral Health at The Warren Alpert Medical School of Brown University, Butler is recognized worldwide as a pioneer in conducting cutting-edge research.