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Date: Sun, 30 Apr 2000 21:40:06 PDT
From: "UPI / ED SUSMAN, UPI Science News" <C-upi@clari.net>
Newsgroups: clari.tw.health.misc, clari.tw.science,
clari.biz.industry.health.care, clari.tw.misc, clari.tw.health,
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Subject: Gene therapy shows promise in brain disease
By ED SUSMAN, UPI Science News
SAN DIEGO, April 30, 2000 (UPI) -- Scientists said Sunday they
have used
gene therapy technology to reverse signs of aging in the brains of
monkeys
and predict that the research might translate into treatment for
Alzheimer's
disease.
"We are now beginning clinical trials to determine whether
nerve growth
factor gene therapy will be useful in combating Alzheimer's disease in
humans," said Dr. Mark Tuszynski, professor of neurosciences at the
University of California, San Diego, at the annual meeting of the
American
Academy of Neurology in San Diego.
"Normal aging in the primate brain is associated with a
decline in both
the function of neurons in the brain, and with their ability to create
connections to other targets in the brain," he said. "Nerve growth factor
gene therapy ameliorates these age-associated declines in neuronal
function.
This finding is of particular interest for the potential treatment of the
most common age-related neurodegenerative disorder, Alzheimer's disease,
in
which neurons atrophy and die."
Tuszynski said that the neurons in the monkey brains were
reduced in size
by 10 percent. When the gene therapy was administered, the cells nearly
returned to normal, showing an average reduction in size of 3 percent.
He
said that change was statistically significant.
Tuszynski said that even if the clinical trials in humans work
well it is
unlikely the treatment would cure Alzheimer's disease, but he said that
it
might be able to delay the deterioration of patients for several years.
About 4 million people in the United States have Alzheimer's
disease and
the number is growing, he said.
"Gene therapy holds immense promise," said Dr. Francis
Kittredge of
Bangor, Maine, president of the AAN. "But there are still a great many
challenges in treating the right patients with the right type of therapy.
We
certainly have a long way to go before we have a practical form of gene
therapy for human brain diseases."
Tuszynski said the human study that to begin this year will
test the gene
therapy procedure on eight patients with early, mild forms of Alzheimer's
disease. They will be evaluated for 18 months and then doctors will
decide
whether to perform a larger study. That won't happen before 2002,
Tuszynski
said.
In the experiments, doctors took a series of skin biopsies
from rhesus
monkeys. The skin cells were then incubated in test tubes, and were
infected
with a virus that had been genetically altered to remove harmful elements
and include a gene that induces the production of nerve growth factor.
The
virus infected the skin cells, and entered the cells nucleus, turning the
cells and their clones into mini-factories that produce the nerve growth
factor. After about three months, the cells had grown enough in volume to
be
implanted into the deep brain of the monkeys.
Tuszynski said that the cells are implanted through a fine
needle that is
guided into place using magnetic resonance and other imaging techniques.
He
said the cells have continued to produce nerve growth factor for at least
a
year. Tuszynski said that in chronic diseases such as Alzheimer's, the
ongoing production of growth factor is desirable. He said in other
conditions proliferation of the growth factor could cause side effects
such
as pain or tumor growth. In 250 experiments with monkeys, Tuszynski said,
there have been no signs of tumor growth, but it remains a theoretical
possibility.
In the study presented at the AAN meeting, Tuszynski reported
on analyses
of the brains of five monkeys. The primates were injected with cells that
were genetically altered.
The procedure would be repeated in the human experiments.
Using patients'
own skin cells should reduce risk of rejection of the cells when
implanted
in the brain.
Even though gene therapy has suffered set backs, including the
death of
patients in some clinical trials, Tuszynski said his protocol was
approved
by the Food and Drug Administration without great debate. "No one has
proposed a gene therapy protocol with as much preliminary primate data as
this one," he said at a news briefing. "This study has a strong
foundation."
Tuszynski said the study should not be construed to be a
treatment to
prevent aging, "but it is not a far stretch to suggest that this may be
useful in the treatment of Alzheimer's disease."
--
Copyright 2000 by United Press International.
All rights reserved.
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