From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Wed Sep 15 1999 - 13:02:43 MDT
CryoNet - Wed 15 Sep 1999
#12417: Aged brain cells restored with gene therapy [Robert Moore]
Subject: Aged brain cells restored with gene therapy
Date: Tue, 14 Sep 1999 05:56:16 PDT
Possible good news for our aging brain cells:
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Aged brain cells restored with gene therapy, researchers say
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 shrunken in elderly Rhesus
monkeys, said Dr. Mark H. Tuszynski of the University of California, San
Diego.
Tuszynski is senior author of a study appearing on Tuesday in the
Proceedings of the National Academy of Sciences.
Tuszynski said that the studies reinforce a new understanding of how the
brain ages and suggests that neurons in the older brain don't die at first,
but actually go into shrunken atrophy.
"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."
He said that 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 actually lost with
age.
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 that the other 60 percent of the
cells had shrunken in size by 10 percent.
But, said Tuszynski, they found the cells were not dead. By inserting genes
for nerve growth into the brain, he said, the cells were revived and
restored to nearly full vigor.
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. He cautioned,
however, "at 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, roughly 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 where then
injected into the forebrain of four of the monkeys. Four others, acting as
controls, got injections of skin cells without the nerve growth factor, or
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.
"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 three
percent," he said.
Tuszynski said it isn't known yet if the restored cells also reinvigorated
the thinking and memory of the old monkeys. That is being tested now in a
new group of old monkeys, he said.
But the therapy is so promising that the researchers last June applied to
the Food and Drug Administration to test the gene therapy technique in
humans with Alzheimer's disease.
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