Aged Brains Renewed By Genes

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."

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 provn, said Tuszynski.

Written By Paul Recer