An initial trial of an antibody therapy that targets Alzheimer's disease has shown promising results and could signal a long-awaited breakthrough in treating the devastating brain disorder that affects over 5 million Americans.
The antibody, known as aducanumab, targets a protein called amyloid beta that builds up in the brain and creates plaques associated with the disease. In a paper published Wednesday in the journal Nature, a trial to evaluate the drug's safety and tolerability showed positive results. Of 165 patients, those who received monthly infusions of the drug for a year showed a significant reduction in amyloid beta and slower cognitive decline than those receiving a placebo.
The therapy is now being tested for efficacy in larger trials. If those are successful, aducanumab could be the first new Alzheimer's drug to be approved in over a decade and the first to reverse signs of the disease.
"Overall, this is the best news that we've had in my 25 years doing Alzheimer's clinical research and it brings new hope for patients and families most affected by the disease," said one of the study's authors, Stephen Salloway, director of neurology in the Memory and Aging program and professor of neurology and psychiatry at Brown University.
Researchers divided recipients into four groups, receiving either a placebo, a low dose of aducanumab, a medium dose or a high dose.
"The higher the dose the larger the degree of reduction, and the longer the treatment, the larger the degree of reduction," said another study author, Roger Nitsch, director at the Institute for Regenerative Medicine at the University of Zurich.
In PET brain scans taken of people receiving the highest dose, "after one year you can see no red on the image, meaning the amyloid has almost completely disappeared," Nitsch said. Compared to past studies, he added, "the effect size of this drug is unprecedented."
Higher doses did result in some adverse reactions among carriers of the APOE4 gene associated with Alzheimer's, including slight brain swelling and bleeding seen in MRI brain scans. But for most recipients this side effect was manageable by careful monitoring and adjusting of the drug, the authors said.
An estimated 5.2 million Americans 65 and older have Alzheimer's, and experts predict that number will nearly triple by 2050 in the absence of new treatments. Five FDA-approved drugs can alleviate some symptoms, but in the past 12 years no new drugs have been approved for the disease, which at $236 billion a year is the most expensive disease in the U.S.
In recent years, several promising therapies have failed to show positive results in later trials. But the technology that can identify amyloid plaques in the brains of living patients — which was used in the new study — has been a game-changer for researchers.
"Before, people (in trials) were screened by cognitive tests and they may or may not have had amyloid," potentially skewing study results, said James Hendrix, director of global science initiatives at the Alzheimer's Association.
"This trial has reinvigorated the field and clearly created a lot more excitement about amyloid as a target," he said of the aducanumab study. "There's been a lot of debate over the last 20 years over the role of amyloid (and) how important it is in the disease." Successful Phase 3 trials of the drug would add strong support for the hypothesis that preventing or clearing amyloid buildup can help patients, he said.
And while experts believe the key to stopping Alzheimer's will ultimately require a combination of approaches, "right now we need one good one, a new one.
"If aducanumab and others in the pipeline have the promise of maybe preventing and slowing down the progression, it could let (people) live out their golden years the way they want to."