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DNA gene vaccine protects against harmful protein of Alzheimer's disease

Doses of DNA-gene-coated gold particles protect mice against a protein implicated in Alzheimer's disease, researchers at UT Southwestern Medical Center have found.

By pressure-injecting the gene responsible for producing the specific protein called amyloid-beta 42 the researchers caused the mice to make antibodies and greatly reduce the protein's build-up in the brain. Accumulation of amyloid-beta 42 in humans is a hallmark of Alzheimer's disease.

"The whole point of the study is to determine whether the antibody is therapeutically effective as a means to inhibit the formation of amyloid-beta storage in the brain, and it is," said Dr. Roger Rosenberg, the study's senior author and director of the Alzheimer's Disease Center at UT Southwestern.

The gene injection avoids a serious side-effect that caused the cancellation of a previous multi-center human trial with amyloid-beta 42, researchers said. UT Southwestern did not participate in that trial. In that earlier study, people received injections of the protein itself and some developed dangerous brain inflammation.

The new study is available online and appears in an upcoming issue of the Journal of the Neurological Sciences.

The researchers used mutant mice with two defective human genes associated with Alzheimer's, genes that produce amyloid-beta 42. "By seven months, the mice are storing abundant amounts of amyloid-beta 42," said Dr. Rosenberg, who holds the Abe (Brunky), Morris and William Zale Distinguished Chair in Neurology.

While the mice were young, the scientists coated microscopically small gold particles with human amyloid-beta 42 genes attached to other genes that program cells to make the protein. The particles were then injected with a gene gun into the skin cells of the mice's ears using a blast of helium.

After receiving 11 injections over several months, the mice showed a high level of antibodies to amyloid-beta 42, and a 60 percent to 77.5
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
29-Mar-2006


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