From: J. R. Molloy (jr@shasta.com)
Date: Tue Sep 14 1999 - 10:23:33 MDT
Study: Gene Therapy Restores Cells
By PAUL RECER
WASHINGTON (AP) _ Aged brains have been restored to youthful
vigor in a gene therapy experiment with monkeys that may soon be
tested in humans with Alzheimer's disease, researchers report.
Scientists hope the treatment will reinvigorate thinking and
memory.
``To our surprise, this technique nearly completely reversed''
the effects of aging on a group of key brain cells that had shrunk
in elderly Rhesus monkeys, said Dr. Mark H. Tuszynski of the
University of California, San Diego.
Tuszynski is senior author of a study appearing Tuesday in the
Proceedings of the National Academy of Sciences.
The studies reinforce a new understanding of how the brain ages
and suggest that neurons in the older brain don't die at first, but
go into shrunken atrophy, he said.
``We've all heard the dogma that we lose 10,000 neurons a day
after the age of 20,'' said Tuszynski. ``Well, that is false. That
doesn't happen.''
An actual count of the cells in the cortex, a key area in the
thinking part of the brain, shows that very few cells are lost with
age, he said.
Instead, he said, his team found that it was control neurons in
another part of the brain, called the basal forebrain, that were
most dramatically affected by aging. These cells, Tuszynski said,
had shrunk in size and had stopped making some regulatory
chemicals, a change that seriously affects the thinking cortex.
``These cells are like the air traffic controllers of the
brain,'' said the researcher. ``They are on the ground, deeper in
the brain, controlling the activities of cells up there in the
cortex. They control the flow of information in the cortex.''
The researchers found that about 40 percent of the basal
forebrain cells could not be detected in old monkeys, and the other
60 percent had shrunk in size by 10 percent.
But the cells were not dead, Tuszynski said. By inserting genes
for nerve growth factor, or NGF, into the brain, he said, the cells
were revived and restored to nearly full vigor.
``We restored the number of cells we could detect to about 92
percent of normal for a young monkey and size of the cells was
restored to within 3 percent,'' he said.
It isn't known yet if the restored cells also reinvigorated the
old monkeys' thinking and memory, but that is now being tested in
another group of old monkeys, he said.
But the therapy is so promising that the researchers applied in
June to the Food and Drug Administration to test the gene therapy
technique in humans with Alzheimer's disease.
If the FDA gives its approval, NGF genes will be injected into
the brains of Alzheimer's patients to see if they will restore some
cognitive powers gradually destroyed by the disease, he said.
Alzheimer's disease does not occur in animals exactly how it
does in humans, said Tuszynski, so the only way to test the gene
therapy technique is in human patients. The early trials, called
Phase I, would involve only a small number to determine safety. It
could be years before the technique's full value is proven, said
Tuszynski.
Dr. Bradley Wise of the National Institute of Aging said the
study is important because it suggests that ``the decline in the
numbers and size of neurons with aging may be reversible.''
``A lot of studies have been done in rats in this area, but this
is a step forward because it used primates (Rhesus monkeys),'' said
Wise. However, he cautioned that ``a lot of work will have to be
done,'' including determining how long the gene treatment lasts,
before the technique could be used routinely in humans.
In their experiment, the University of California, San Diego
researchers used eight monkeys with an average age of 23, the
monkey equivalent of the late 60s to 70s in humans.
Skin cells were taken from each of the monkeys. Into these
cells, the researchers inserted a gene that makes human nerve
growth factor, an essential chemical found in the brain. The
modified cells were then injected into the forebrain of four of the
monkeys. Four others, acting as controls, got injections of skin
cells without the NGF gene.
Once in the brain, the modified cells began making NGF.
After three months, the researchers examined the brains of the
eight monkeys. The control monkeys showed a brain cell loss
expected for animals their age. But the brains of the monkeys with
the NGF genes injections had an almost youthful appearance, said
Tuszynski.
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