New hope for Alzheimer’s vaccine

Researchers have discovered a way to refine an experimental Alzheimer’s vaccine, a finding that could pave the way for new treatment and prevention of the debilitating disease that affects people’s ability to think and recall information. Alzheimer’s occurs when toxic biochemical compounds known as amyloid-beta peptides accumulate in the brain, forming plaque deposits and injuring nerve cells, which eventually causes dementia. In 2000, researchers at the Centre for Research in Neurodegenerative Diseases published a paper showing how the amyloid-beta peptide vaccine blocked the production of the plaques and reversed learning impairment. The vaccine stimulates the body’s immune system into forming antibodies against the plaques in the brain, but it also caused inflamation. This new research claims to have found a way to better isolate the active epitope detected by antibodies. After testing a more refined, targeted amyloid-beta vaccine on mice, the scientists found that the antibodies generated by the vaccine cleared away the plaques — improving cognitive function in the mice and leaving no evidence of brain inflammation.

From the University of Toronto:New hope for Alzheimer’s vaccine
Refined vaccine circumvents brain inflammation in mice
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Nov. 1, 2002 — U of T researchers have discovered a way to refine an experimental Alzheimer’s vaccine, a finding that could pave the way for new treatment and prevention of the debilitating disease that affects people’s ability to think and recall information.

Alzheimer’s occurs when toxic biochemical compounds known as amyloid-beta peptides accumulate in the brain, forming plaque deposits and injuring nerve cells, which eventually causes dementia. In 2000, researchers at the Centre for Research in Neurodegenerative Diseases published a paper showing how the amyloid-beta peptide vaccine blocked the production of the plaques and reversed learning impairment.

The vaccine stimulates the body’s immune system into forming antibodies against the plaques in the brain. Human trials have been under way for some time in Europe and the U.S. but were halted earlier this year when some patients developed inflammation of the brain.

However, in the October issue of Nature Medicine, U of T researchers demonstrated how to circumvent the brain inflammation in mice. Led by Professors JoAnne McLaurin and David Westaway of laboratory medicine and pathobiology and Professor Peter St. George-Hyslop, director of CRND, the study identified the active epitope — a piece of the peptide — detected by antibodies in the immune system once the vaccine is administered.

They found that only a segment of the vaccine produced the beneficial immune response, suggesting that a small portion of the vaccine would be less likely to cause the inflammation in humans. After testing a more refined, targeted amyloid-beta vaccine on mice, the scientists found that the antibodies generated by the vaccine cleared away the plaques — improving cognitive function in the mice and leaving no evidence of brain inflammation.

According to McLaurin, the study, funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada, could also lead to small-molecule drugs that could bypass the problematic side-effects of immunotherapy.

“This information gives new hope for the development of a vaccine for Alzheimer’s disease,” McLaurin said. “If side effects persist then the development of a small molecular mimic will circumvent immunotherapy completely.”

In a related study published in the same issue of Nature Medicine, Swiss researchers showed that the human patients actually did accumulate antibodies against A-beta — a critical step in plaque clearance. They also found that the antibodies that formed did not attack normal brain cells. Taken together, the researchers say the two studies offer critical evidence for future research for an Alzheimer’s vaccine.

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