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Effects of gene therapy seen in aging monkeys
Shrinking neurons respond to injections of human growth factor
  
By Roberta Friedman

Scientists used gene therapy to deliver a restorative growth factor to the brains of aging rhesus monkeys. Injections of the growth factor reached the target cells in the animals' brains, and they appeared to rejuvenate the shriveling nerve fibers seen in aging, according to Mark H. Tuszynski, of the University of California at San Diego, and colleagues.

"Regardless of the mechanism of age-related atrophy and loss in neuronal systems, growth-factor delivery reverses these changes in the primate basal forebrain," the investigators report, adding that the findings support "a potential rationale for growth-factor delivery in the context of such neurodegenerative disorders as Alzheimer's disease." At least two individuals with Alzheimer's have enrolled in a planned clinical trial to test the safety of the procedure.

The researchers injected cells engineered to express the human gene for nerve growth factor into the region of the monkey brain that houses cholinergic neurons, which are targets of existing therapies for Alzheimer's disease. The strategy of placing growth factors at the source of the brain deficit—the clusters of nerve cell bodies—can apparently prod distant production and maintenance of appropriate connections where the nerve fibers terminate.

In the monkeys, aging caused a 25 percent loss in the network of cholinergic nerves to the cortex. Although the input to the cortex is diminished, the cells might still be alive. The neurons themselves are not lost, but rather, their branches are pruned. The gene therapy restored neurotransmitters maintained by the cholinergic neurons in the outer layers of the brain, the site of short-term memory and intellectual processing. The findings appeared in Proceedings of the National Academy of Sciences.

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Conner, J.M. et al. Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation. Proc Natl Acad Sci USA 98, 1941-1946 (February 13, 2001).
 

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