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New Hope for Old Brains


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April 30, 2000 (San Diego) -- Transplanting brain cells that have been genetically engineered to churn out a nerve cell-stimulating chemical may one day be used to help people with Alzheimer's disease, according to research presented here Sunday at the 52nd annual meeting of the American Academy of Neurology. University of California, San Diego (UCSD), researcher Mark Tuszynski, MD, PhD, reported on work measuring aging in the brains of rhesus monkeys and a gene therapy experiment that reversed age-related changes.

The results of the gene therapy experiment in animals were so strong, says Tuszynski, that he and his colleagues submitted a proposal to the FDA to study the technique in humans. The agency approved his plan, and eight patients with early Alzheimer's disease are being recruited for a study that's expected to begin this summer.

Although aging and Alzheimer's disease are not the same, some of the features, such as decline in memory and other thinking functions, occur in both. In addition, as one ages, the risk of getting Alzheimer's disease increases.

In his first experiment, Tuszynski discovered that so-called cholinergic nerve cells deep in the brain waste away as a monkey grows older. This is the same kind of thing that occurs in Alzheimer's in humans. Comparing old and young adult monkeys, he found a decrease in nerve cell density of nearly 30%.

The results of the second experiment were reported at the ongoing meeting. Tuszynski and colleagues injected five animals with some of the animals' own skin cells, which had been genetically engineered to secrete a chemical called nerve growth factor.

In addition to nourishing the nerves, nerve growth factor helps maintain the nerve connections to other parts of the brain, such as those areas involved with intellectual activities and memory. (These are areas that are severely affected by Alzheimer's disease.)

Tuszynski and his colleagues at UCSD's center for neural repair found that the size of the cholinergic neurons had been restored significantly.

"This is an area that is growing and is very close to human application," says Michael E. Selzer, MD, professor of neurology at the University of Pennsylvania and chairman of the academy's section on neural repair and rehabilitation.

In Alzheimer's, it's not clear whether these cells simply atrophy (shrivel), or whether they die. "If they're dead, it may be too late," says Selzer. "But if many of them are in the process of dying and they are dependent on nerve growth factor for robust survival, then it may still be that this sort of gene therapy will have a beneficial effect."

It will take about a year and a half to know whether the gene therapy is safe in humans with early Alzheimer's disease. If it is, Tuszynski expects a second trial to evaluate the effectiveness of the treatment to begin in 2002. Since monkeys do not develop Alzheimer's, he says, he does not know for certain that thinking and memory in humans will improve with the therapy. However, earlier studies with rats did show an improvement in memory.

How long the effects of gene therapy will last is another unknown. "Gene therapy will not be a cure for Alzheimer's," says Tuszynski, "but it may delay progression or prevent its occurrence for several years."

 

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