May 2, 2000 Age-related deterioration in critical brain networks may be restored by gene therapy, according to a study in monkeys presented at the American Academy of Neurology's 52nd Annual Meeting in San Diego, CA, April 29 -- May 6, 2000. This finding lends support to a study just underway to treat Alzheimer's disease using a similar gene therapy approach, say the study's authors.
Researchers from the University of California in San Diego found that normal aging in monkeys causes a 28 percent decline in the density of certain brain networks originating from nerve cells called neurons deep in the brain.
The scientists found that they were able to restore these connections by transplanting brain cells genetically programmed to release a protein called "nerve growth factor."
"It would be inappropriate to suggest that this approach could be used to treat the course of normal aging, but it is not a far stretch to suggest that this may be useful in the treatment of Alzheimer's disease," said Mark Tuszynski, MD, PhD, a researcher at the Center for Neural Repair at UCSD and principal author of the report. "Indeed, we are now beginning clinical trials to determine whether nerve growth factor gene therapy will be useful in combating Alzheimer's disease in humans."
Nerve growth factor nourishes neurons and allows brain cells to grow and maintain fibers called axons that link neurons in one area to neurons in other areas of the brain.
In previous studies, Tuszynski's group found that the normal aging process involves atrophy and a loss of function within a particular set of brain cells deep in the brain known as cholinergic neurons.
These cells, which are connected by axon connections to the outer layers, or cortex, of the brain, are believed to be critical to many of the memory and other mental functions that deteriorate gradually and to a mild degree with age, but much more rapidly and severely in Alzheimer's disease.
Indeed, other researchers have shown that the cholinergic neurons are particularly hard hit by Alzheimer's disease.
Tuscynski's group measured the density of cholinergic axons in the cortex, comparing the brains of normal aged monkeys with aged monkeys that had received transplants of brain cells engineered to produce large amounts of nerve growth factor.
"We show that we can reverse these age-related losses of connections in the cortex by delivering nerve growth factor to cell bodies deep within the brain," said Tuszynski.
The next steps, said Tuszynski, are to determine whether nerve growth factor gene therapy actually improves mental function in aged monkeys and to proceed with clinical trials to determine if this therapy is safe and effective in humans with Alzheimer's disease.
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