From New Orleans, at the annual meeting of the Society for Neuroscience
Investigators are testing whether an antibiotic that manufacturers pulled from the U.S. market several decades ago for safety concerns can slow or prevent Alzheimer’s disease.
Many neuroscientists believe that a buildup in the brain of a protein fragment called beta-amyloid causes Alzheimer’s disease. Over the past few years, Ashley T. Bush of the Massachusetts General Hospital in Boston and his colleagues have gathered evidence that copper and zinc in the brain promote beta-amyloid accumulation. In test tubes, for example, zinc triggers beta-amyloid molecules to form insoluble masses. In a study last year, the researchers even reported that chelating agents, which trap and remove metals from tissues, dissolve beta-amyloid in brain tissue taken from people who had died of Alzheimer’s disease.
A screen of existing drugs for ones with chelating properties turned up clioquinol, an antibiotic that sops up zinc and copper, says Bush. In two studies of mice genetically engineered to overproduce beta-amyloid, he and his colleagues have now shown that the antibiotic reduces amyloid deposits in the brain.
One-third of young mice treated with clioquinol didn’t develop detectable amyloid deposits; the others had far fewer than untreated mice did. In old mice with established amyloid deposits, a 9-week regimen of the antibiotic reduced brain beta-amyloid by 50 percent, compared with untreated rodents.
In collaboration with Australian scientists, the Boston researchers have begun testing clioquinol on people with mild-to-moderate Alzheimer’s. They plan to monitor the volunteers for serious vitamin B12 deficiency, the rare side effect that led to the antibiotic’s U.S. withdrawal in the 1970s.