Newsweek

FALSE STARTS

Dr. Eric Reiman can’t reveal the identity of the 73-year-old woman from a rugged mountain town outside Medellin, Colombia, who arrived at Boston’s Logan Airport a couple of years ago for tests at Harvard Medical School. But he will say this: Finding her may well be among the most surprising developments to emerge from a nearly three-decade-long study of Colombians cursed with a gene that usually dooms its victims to full-blown Alzheimer’s disease by the age of 50.

What made the woman special was not just what doctors discovered when they first scanned her brain to measure the buildup of amyloid-beta, the sticky plaques long suspected of playing a key role in the devastating cognitive decline seen in advanced Alzheimer’s disease. She had the highest levels they’d ever recorded. What made the woman so special was that—despite those plaques—she seemed almost normal for her age.

“Nobody’s at higher risk for Alzheimer’s than she would have been,” says Reiman, a neuroscientist at the Banner Alzheimer’s Institute in Phoenix, who has spent the last three decades studying the loosely related, 6,000-person family cohort she belongs to in Colombia. “But she developed mild cognitive impairment about three decades after the average age in her family. And she still hasn’t developed Alzheimer’s dementia.”

The Colombian woman’s case is a potent testament to both the tantalizing promise—and the enormous frustration—that have come to characterize the pursuit of drugs to treat Alzheimer’s disease. In two decades, the pharmaceutical industry has spent $600 billion in pursuit of drugs, focusing with almost single-minded intensity on compounds designed to safely reduce or prevent the buildup of deadly plaques that are one of its primary hallmarks.

Attacking plaque is precisely the point of the new Alzheimer’s drug aducanumab, made by the drug maker Biogen, which was being tested in two separate clinical trials. High-ranking officials at the U.S. Food and Drug Administration have supported the drug and recently called preliminary trial results “highly persuasive.” But in early November, a panel of independent experts, convened by the FDA to review data from ongoing trials, contradicted this assessment. They cited conflicting data—one trial showed a mild therapeutic effect, another trial showed none—and a lack of efficacy. “The totality of the data does not seem to provide sufficient evidence” of effectiveness, declared one of the FDA’s own statisticians in a report.

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