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Gene Vaccine for Alzheimers Shows Promising Results
Dec. 14, 2004 - For years scientists have examined
the possibility of using a protein-based vaccine to slow the progression
of the disease in its early stages. Now, researchers have created a
gene-based vaccine aimed at stimulating the immune systems of mice to
potentially fight off amyloid protein in the brain that cause the
devastating plaques that are characteristic of Alzheimer's disease.
Their findings by UT Southwestern Medical Center at
Dallas researchers appear in today's issue of the Archives of
Neurology.
"Previous Alzheimer's vaccines were protein-based," said Dr. Baoxi Qu,
the study's lead author and assistant professor in the Center for
Biomedical Inventions and internal medicine. "We wanted to try a
DNA-based genetic vaccine instead to see if we could enhance the immune
response."
Although prior studies of amyloid protein
vaccination had shown some slowing in the plaque buildup, negative side
effects also occurred in a handful of patients. Some had autoimmune
responses that caused encephalitis.
The key in the UT Southwestern study was finding
another way to vaccinate patients without stimulating the body's own
immune cytotoxic T cells, said Dr. Roger Rosenberg, a study author and
director of the Alzheimer's Disease Center.
"This dilemma was discussed with my colleagues, and
we decided to try vaccination with an amyloid gene, rather than the
amyloid protein vaccine," said Dr. Rosenberg.
The UT Southwestern researchers vaccinated mice
with a "gene gun." The gene gun and gene-vaccination technologies were
invented by Dr. Stephen Albert Johnston, director of the Center for
Biomedical Inventions and senior author of the latest study.
"We have been developing ways to use
gene-immunization to manipulate the immune response," Dr. Johnston said.
"This study was the first step to see if we can apply these techniques
to create a safe and effective Alzheimer's vaccine."
Said Dr. Rosenberg: "When we vaccinated the mice
with the mouse form of the amyloid gene, they made lots of antibodies
without stimulating cytotoxic T cells. When we get to human studies, we
hope to show that humans can make human antibodies against the amyloid
as well."
Current treatments for Alzheimer's disease focus on
the symptoms since no therapies have been clinically proven to slow or
prevent progression of the disease. Amyloid protein deposits are present
in the early phase of the disease a fact that suggests a gene
vaccination would be a step forward in slowing the progression of
dementia.
From the mouse studies and in previous clinical
trials of patients with Alzheimer's disease, immunization with amyloids
slowed the buildup of plaque on the brain and appeared to slow cognitive
loss.
"Although human clinical trials are still at least
two years out, theoretically, we are on the right track," he said.
Other UT Southwestern authors involved in the study
were Dr. Liping Li, a research fellow in the Center for Biomedical
Inventions; and Dr. Philip Boyer, assistant professor of pathology.
The study was supported in part by National
Institute on Aging and the Rudman Foundation.
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