Jefferson Alzheimer's vaccine shows promise in animal model

"The amyloid in the brain seemed to be bound up to antibodies in the blood and cleared away," Dr. Gandy says. "We're clearly mimicking the biochemistry in the monkey that we have seen in mice. Vaccinating with amyloid brings an immune response that stimulates removal of amyloid from the body."

"The animal model described in this study expands the way we might evaluate new vaccine products," says William Thies, Ph.D., Alzheimer's Association vice president for medical and scientific affairs.

There was no evidence of inflammation in the monkey brains six months later.

According to Dr. Gandy, researchers in the late 1990s created a transgenic Alzheimer's mouse with human genes. They vaccinated the mice with beta-amyloid and found a dramatic clearing of the amyloid plaques. They also found they could prevent plaque formation if they began vaccinating before plaques formed, and could reduce plaque formation if the vaccine was given early in their development. In addition, the researchers found they could also take serum from vaccinated mice, put it in unvaccinated mice and stimulate clearance of plaques.

But in a subsequent clinical trial of 300 patients, 15 developed encephalitis, or inflammation of the brain, from an immune reaction in the brain. "The individuals developed antibodies that caused excessive brain inflammation in being drawn to the amyloid plaques and activating clearing from the brain the inflammatory response was out of control," says Dr. Gandy.

"We'd like to dissociate the good part of the immune response from the bad part," Dr. Gandy says.

Dr. Gandy notes that a cellular response by T-cells and not the antibodies could have caused the encephalitis. "It might be possible to design a different vaccine or design synthetic antibodies to avoid the encephalitis problem," he says.

Dr. Gandy and his team curre

Contact: Steven Benowitz
Thomas Jefferson University

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