The first tests in people of a vaccine that may slow or prevent the devastation of Alzheimer's disease have so far shown that the approach is safe, scientists announced this week at a Washington, D.C., meeting. It's still too early to gauge whether the vaccine actually works, however, say the researchers.
Newly reported animal tests added to the cautious optimism about the new vaccine strategy. In mice genetically engineered to develop brain lesions similar to those seen in Alzheimer's disease, the vaccine averted expected declines in certain memory and learning skills.
Last year, Dale Schenk of Elan Pharmaceuticals in South San Francisco stunned neuroscientists with the news that simply injecting such mice with a protein fragment called beta-amyloid keeps naturally-occurring amyloid from accumulating in the brains of the rodents and even eliminates preexisting amyloid deposits known as plaques (SN: 7/10/99, p. 20: http://www.sciencenews.org/sn_arc99/7_10_99/fob1.htm).
Many scientists believe that the abnormal buildup of amyloid brings about Alzheimer's disease, and Elan's vaccine offers the first possible treatment for this apparent root cause of the illness.
The vaccine elicits antibodies that bind to beta-amyloid. While the antibodies generally circulate in the bloodstream, some apparently leak across the blood-brain barrier. Once in the brain, the antibodies seem to mark amyloid plaques for clearance by microglia, which are immune cells that patrol the brain.
At this week's World Alzheimer Congress 2000, Schenk offered new evidence to support this theory. He and his colleagues added microglia to slices of rodent brain tissue riddled with amyloid plaques. The immune cells took up the amyloid, but only if the researchers also introduced antibodies that bind to beta-amyloid. The microglia then degraded the protein fragments. "The amyloid literally disappears," says Schenk.
Some scientists have expressed concern that stimulating anti-amyloid responses will itself lead to brain damage. To address that issue, the Elan team examined the vaccine's safety in mice, guinea pigs, rabbits, and rhesus monkeys. "We saw virtually no signs of problems in the animals," says Schenk.
These encouraging results prompted Elan to begin safety tests on people with mild-or-moderate Alzheimer's disease. The researchers recently completed tests on 24 patients in the United States, who each received a single injection of beta-amyloid. No obvious side effects have emerged. "There's no question the vaccine was well tolerated," says Schenk.
To determine the vaccination schedule that induces the strongest antibody response, Elan has started a new trial in England, where about 80 people will receive multiple injections of beta-amyloid. If that trial confirms the safety of the vaccine, the company plans in 2001 to start trials designed to reveal whether the vaccine actually arrests, or even reverses, Alzheimer's disease.
"Our first goal is to block further progression" in Alzheimer's patients, says Schenk. "We don't know if they will recover."
Other scientists at the meeting reported they had confirmed and extended Elan's initial mouse study. Christopher G. Janus of the University of Toronto and David G. Morgan of the University of South Florida in Tampa each described immunizing genetically engineered mice that normally develop amyloid plaques and lose memory and learning skills. Janus' vaccinated mice actually improved their performance on one maze test; Morgan's immunized rodents didn't acquire the same memory problems with age as his untreated animals did.
Bill Thies, the Alzheimer's Association vice president of medical and scientific affairs, calls Janus' and Morgan's results "very significant" but also expresses caution about their relevance to people. "It's very hard to look at mouse behavior and compare it to Alzheimer's disease," he says.
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