X-Message-Number: 12417
From: "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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