Researchers are giving drugs to healthy people in hope of clearing away toxic proteins in the brain and warding off neurodegeneration.
, it was recognizing this long-term picture: that the drug’s ability to remove amyloid-β made it likely that it could reduce Alzheimer’s symptoms down the line. Biogen’s large, placebo-controlled trials of aducanumab in people with mild Alzheimer’s had not unambiguously improved their clinical symptoms, but the drug did a good job of clearing amyloid plaques from their brains. The agency declared that aducanumab was the first treatment to affect the biological cause of the disease.
Many researchers agree that the best test of the hypothesis — and the best way to stop the disease in its tracks — is to give people these drugs early, without waiting for Alzheimer’s symptoms to set in first.According to Hardy, designers of even the earliest trials might have realized that they were recruiting too late in the disease. “Through the retrospectoscope, it was clear — the data were already there,” he says.
But the results of the trial, announced in 2020, were disappointing. The trial failed to prove that the drugs could slow cognitive decline — although there was little decline in treated presymptomatic participants, there was also little decline in the placebo group. “That meant that we were simply unable to say whether the drugs would eventually help an asymptomatic population or not,” says Randall Bateman at Washington University School of Medicine in St.
That presented Reiswig with a dilemma. When he was originally tested for the gene mutation, he had chosen not to be informed of the result. But the extension of the study was only available to mutation carriers, so a request to participate would automatically reveal his genetic status. “I decided it was time for me to know, but I planned things carefully,” he says. He retreated to a holiday rental in Colorado with his wife to receive the phone call from his genetic counsellor.
Outside the DIAN consortium, other trials for early-onset Alzheimer’s are under way, testing drugs in people who already have some amyloid build-up. Genentech–Roche is studying individuals from a large family in Colombia, half of whom carry a pathological mutation in a gene that encodes part of one of the amyloid-chopping secretase enzymes. Its trial of the drug crenezumab will finish this year. Studies are also gearing up to test Alzheimer’s drugs in people with Down’s syndrome.
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