Treatment reduced brain plaques, but effects on mental function not clear
J. Sevigny et al/Nature 2016
An experimental drug swept sticky plaques from the brains of a small number of people with Alzheimer’s disease over the course of a year. And preliminary results hint that this cleanup may have staved off mental decline.
News about the new drug, an antibody called aducanumab, led to excitement as it trickled out of recent scientific meetings. A paper published online August 31 in Nature offers a more comprehensive look at the drug’s effects.
“Overall, this is the best news that we’ve had in my 25 years doing Alzheimer’s clinical research,” study coauthor Stephen Salloway of Brown University said August 30 at a news briefing. “It brings new hope for patients and families most affected by the disease.”
The results are the most convincing evidence yet that an antibody can reduce amyloid in the brain, says Alzheimer’s researcher Rachelle Doody of Baylor College of Medicine in Houston, who was not involved in the study.
Still, experts caution that the results come from 165 people, a relatively small number. The seemingly beneficial effects could disappear in larger clinical trials, which are under way. “These new data are tantalizing, but they are not yet definitive,” says neuroscientist John Hardy of University College London.
Like some other drug candidates for Alzheimer’s, aducanumab is an antibody that targets amyloid-beta, a sticky protein that accumulates in the brains of people with the disease. Delivered by intravenous injection, aducanumab appeared to get inside the brains of people with mild Alzheimer’s (average age about 73) and destroy A-beta plaques, the results suggest. After a year of exposure to the drug, A-beta levels had dropped. This reduction depended on the dose — the more drug, the bigger the decline in A-beta. In fact, people on the highest dose of the drug had almost no A-beta plaques in their brains after a year.
“I know of no other antibody that leads to this degree of amyloid removal,” study coauthor Alfred Sandrock of Biogen in Cambridge, Mass., said at the news briefing. For several decades, scientists have been trying to figure out whether A-beta is a cause, or just a symptom, of Alzheimer’s (SN: 3/12/11, p. 24). With its ability to reduce A-beta plaques in the brain, aducanumab may help settle the debate.
The bigger question is whether the drug can preserve thinking skills and memory. The new study was not designed to detect improvements in mental performance. Yet it turned up hints that aducanumab may help.
Compared with participants who received a placebo, people who took aducanumab showed less decline on standard tests of memory and thinking skills over the course of a year. And like the reductions in brain amyloid, better performance seemed to come with higher doses. During the study, people who received the placebo lost just under three points on average on a 30-point cognitive test. In contrast, people on the highest dose of aducanumab lost a little over half a point.
“One needs to take the cognitive data with a grain of salt at the moment, given the small number of people who enrolled and completed the study,” says neuroscientist Eric Reiman of the Banner Alzheimer’s Institute in Phoenix. But if larger studies show a similar benefit, “it would be a game changer for the field,” says Reiman, who wrote an accompanying commentary in Nature.
Aducanumab targets several forms of A-beta — including both small, soluble bits called oligomers and larger clumps called fibrils — that make up plaques. Both forms may cause trouble. Once aducanumab sticks to A-beta, specialized brain cells called microglia may come in and remove the buildup, lab experiments suggest.
Twenty-seven people in the study had an adverse drug reaction known as ARIA, marked by changes in brain fluid detected by brain scans. The side effect is often without symptoms, but can cause headaches or more serious trouble in some people. ARIA was more common at higher doses, the researchers found. The larger studies of aducanumab that are under way may help scientists pinpoint the most effective dose with the fewest side effects.
J. Sevigny et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. Vol. 537, September 1, 2016. doi: 10.1038/nature19323.
E. Reiman. Attack on amyloid-βprotein. Nature. Vol. 537, September 1, 2016.
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