It's hard to think of an illness more devastating, or less treatable, than Alzheimer's. It afflicts 4 million Americans--one in 10 of those over 65, nearly half of those over 85--and the toll is rising as the population ages. Despite two decades of intensive research, no one knows quite how the brain-killing condition arises, let alone how to arrest it. Small wonder, then, that a preliminary study published in last week's Nature is provoking such excitement. Researchers at Elan Pharmaceuticals of South San Francisco showed that--in mice, at least--an experimental vaccine can prevent and even reverse some of the brain lesions that are hallmarks of Alzheimer's. The vaccine may yet prove worthless, or even harmful, in people. But the possibilities it raises are dazzling.
The basic idea is simple. Alzheimer's disease involves a buildup of so-called amyloid plaques within critical regions of the brain. No one knows just how these sticky protein deposits affect mental function, but they're strikingly abnormal, so the Elan researchers set out to mobilize the immune system against them. The vaccine they devised combines the main constituent of plaque--a protein fragment called beta amyloid--with a substance known to excite the immune system. If the concoction provoked a reaction against beta amyloid, the scientists reasoned, it might block the formation of plaques.
That's exactly what happened when they tested it in plaque-prone mice. In the first of two experiments reported last week, the researchers gave young mice repeated injections of the vaccine or one of several formulations that lacked the protein fragment. By the time the mice were 13 months old, those in the control groups had plaques covering 2 to 6 percent of their brains, yet the immunized animals remained virtually plaque-free. In the second experiment, the researchers used mice that were already old enough (11 months) to exhibit significant plaques. Over a seven-month period, the control animals suffered a 17-fold increase in plaque, while those receiving the vaccine showed a decrease of more than 99 percent. "We were completely blown away," says Dale Schenk, the Elan pharmacologist who led the study.
Will the vaccine do anything for people? Before they even try to find out, researchers will have to assess its safety. There were no signs of toxicity in the mouse studies, but if humans reacted differently, the treatment could cause brain inflammation, or trigger immune reactions against healthy tissue. Schenk and his colleagues hope to launch a small safety study among Alzheimer's patients later this year, then start testing for efficacy. If everything went perfectly, doctors could be administering the vaccine six years from now, both to treat Alzheimer's and to prevent it in people at high risk.
But there are reasons not to get too excited. As cancer researchers have learned, it's hard to sustain a vigorous immune response to something that isn't foreign to the body. Just as our immune systems tend to tolerate tumor cells, they may respond only briefly or halfheartedly to the amyloid vaccine. And even if the vaccine works as intended, it may not vanquish Alzheimer's, for plaques are not the only hallmark of the disease. Unlike the mice in last week's study, Alzheimer's sufferers exhibit both plaques and "tangles," twisted proteins found inside brain cells. Some experts suspect that tangles are what ruin people's minds, and that plaques are merely a byproduct. If this new approach to treatment succeeds only in resolving that issue, it will stand as a landmark.