Researchers target Alzheimer’s gene vaccine

June 05, 2006

A gene vaccine that prevents buildup of a specific protein in the brain may spell progress in the fight against Alzheimer's disease. A hallmark of Alzheimer's disease is the accumulation in the brain of the protein amyloid-beta 42. Scientists at the Biodesign Institute at ASU are partners in research that found that mice vaccinated with the gene responsible for amyloid-beta 42 produced antibodies that greatly reduced the protein's build-up in the brain.<separator></separator>“Our approach is trying to take advantage of the unique capabilities of gene vaccines to create a safe Alzheimer's vaccine,” says Stephen Albert Johnston, director of the Center for Innovations in Medicine at the Biodesign Institute and co-inventor of gene vaccines.<separator></separator>The new study is available online at the Web site (<a href="http://www.elsevier.com/locate/jns">www.elsevier.com/locate/jns</a>), and it will appear in an upcoming issue of the Journal of the Neurological Sciences. <separator></separator>Johnston joined the Biodesign Institute in June of 2005 from the University of Texas Southwestern Medical School. Johnston, along with his colleagues at UT Southwestern, are the first to demonstrate that gene vaccination can reduce amyloid-beta 42 levels in an animal model of Alzheimer's disease. Levels of the protein, which is found to accumulate in Alzheimer's disease, were reduced by 60 percent to 78 percent.<separator></separator>“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,” says Roger Rosenberg, the study's senior author and director of the Alzheimer's Disease Center at UT Southwestern.<separator></separator>The researchers used mice with two defective human genes associated with Alzheimer's, genes that produce amyloid-beta 42. These animals develop numerous amyloid plaque deposits, the pathological signature of Alzheimer's disease, by 7 months of age.<separator></separator>“By 7 months (old), the mice are storing abundant amounts of amyloid-beta 42,” Rosenberg says.<separator></separator>In the study, the Alzheimer's mice were genetically immunized by coating microscopically small gold particles containing a cocktail of the human amyloid-beta 42 genes. The particles then were injected with a gene gun into the skin cells of the mice's ears.<separator></separator>After receiving 11 injections over several months, the mice showed a high level of antibodies to amyloid-beta 42, and significantly cleared out the peptide from their brains.<separator></separator>For the control group, the researchers used a related but harmless protein, amyloid-beta 16, or with a gene vaccine that lacked any amyloid genes. These treatments did not cause antibody production, and the mice showed the large amounts of amyloid-beta 42 brain plaques normally seen in Alzheimer's mice.<separator></separator>The gene injection showed superior results compared to a previous human study in which amyloid-beta 42 protein itself was injected into muscle, Rosenberg says. That study was halted when a small percentage of participants developed inflammation of the brain and spinal cord.<separator></separator>In contrast, injecting the gene caused no brain inflammation in the mice.<separator></separator>Johnston's gene immunization approach is undergoing further studies, with the ultimate goal being a clinical trial in humans.<separator></separator>“These results are an important step in our ongoing effort to produce a safe gene vaccine to prevent or relieve existing Alzhiemer's disease,” Johnston says.<separator></separator>Other UT Southwestern researchers involved in the study are Bao-Xi Qu, an assistant professor of neurology, Philip Boyer, an assistant professor of pathology, and Linda Hynan, an associate professor of clinical sciences and psychiatry.<separator></separator>The work was supported by the National Institute on Aging, the National Alzheimer's Coordinating Center, the Rudman Foundation, the Luttrell Foundation, UT Southwestern's Winspear Family Special Center for Research on the Neuropathy of Alzheimer's Disease and royalty income to Johnston.<separator></separator>