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Alzheimer News 5/11/2005
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Final analysis: First vaccine trial is hopeful but inconclusive

Two reports in the May Neurology close the book on one of the most closely watched stories in Alzheimer science: the first clinical trial of a drug targeting beta-amyloid, a protein fragment considered a prime suspect in the disease's devastating brain damage. The story ends on a note of guarded optimism.

The trial had to be stopped prematurely in 2002 before participants received all their planned doses because the drug, AN-1792 or "the Alzheimer vaccine," caused brain inflammation in about six percent of recipients. Since the vaccine mobilized the immune system against beta-amyloid, its effects persisted after the trial ended, and scientists continued to monitor participants for a year after they stopped administering the drug. Their primary goal was to learn more about the vaccine's safety, but they also tracked effects on memory, thinking and overall function. These Neurology reports summarize those observations, many of which were previously reported at the Alzheimer's Association 9th International Conference on Alzheimer's Disease and Related Disorders and other professional meetings.

"Although there was no dramatic benefit on any single benchmark, there were enough small hopeful signs on a variety of measures to sustain interest in this approach to treatment," says William H. Thies, Ph.D., Alzheimer's Association vice president, medical and scientific affairs. "Several teams are already looking at strategies to trigger a robust immune response to beta-amyloid without mobilizing the parts of the immune system involved in inflammation. Another noteworthy result of this trial is the laboratory work, pathology and brain imaging all show the vaccine had a profound physical impact on the brain. Whether or not this approach turns out to be the right one, demonstrating that kind of effect is an extremely important proof of concept."

Key trial findings include:

  • Vaccine recipients did not fare any better than those who took the placebo on the trial's chief tests of memory, thinking and overall function. However, vaccine recipients who developed the highest levels of antibodies to beta-amyloid declined less in their average performance on an additional battery of nine tests of mental function and their scores actually improved slightly on a few of the specific tests.

  • Brain autopsies of a few participants who died since receiving the vaccine showed lower-than-expected levels of plaques, the abnormal deposits formed by beta-amyloid.

  • Some study participants agreed to undergo spinal taps in exchange for a slightly greater chance of getting the vaccine rather than the placebo. In those who developed the highest levels of antibodies, these spinal taps have shown reduced levels of a protein called tau (pronounced to rhyme with "wow.") Tau is involved in tangles, a pathological structure considered the other hallmark Alzheimer abnormality along with amyloid plaques. Plaques and tangles are widely believed to be related to one another, although the nature of the relationship is not known. The fact that AN-1792 also lowers tau by targeting beta-amyloid could be another signal of its effectiveness.

  • Magnetic resonance imaging (MRI) studies showed that vaccine recipients with high antibody levels experienced significantly more brain shrinkage than those with lower levels. This finding was unexpected because over time, the brain of an individual with Alzheimer's shrinks dramatically. A treatment that blocked the disease's destructive effects would be expected to prevent or reduce shrinkage. A further puzzle is that the higher level of shrinkage was not accompanied by the greater decline in function that would normally be expected. Scientists are not yet certain how to interpret the imaging data.

For more information, please see:

  • The Alzheimer's Association fact sheet on treatments targeting beta-amyloid and the amyloid hypothesis

 

Alzheimer's Association

Our vision is a world without Alzheimer's
Formed in 1980, the Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research.