Study: Gene Therapy Restores Cells

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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