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Neuron savers: gene therapy slows Alzheimer's disease.

Putting extra copies of the gene for a cellular growth factor into the brains of people with Alzheimer's disease slows the degenerative condition, a new study suggests.

Alzheimer's disease kills neurons, the brain cells that orchestrate message signaling throughout the nervous system. The gene added in this study encodes nerve growth factor (NGF), a protein that keeps these cells alive and so facilitates signaling among them.

The vehicle for the human gene was the patients' own skin cells. Researchers took a bit of skin tissue from each of eight people diagnosed with early Alzheimer's disease and used a non-replicating virus to transfer genes for human NGF into the skin cells.

The scientists then injected these genetically modified cells into each patient's brain. However, two of the patients were excluded from the study soon after that surgery because of bleeding in their brains.

Over the next 2 years, positron-emission tomography scans of the other patients revealed increased metabolic activity in their brains, a sigaa of neuron rejuvenation. An autopsy on one of the excluded patients, who died of a heart attack during the study, revealed that the implanted cells were making NGF. Nearby neurons appeared healthy.

These biological findings paralleled changes in the patients' behavior. Although standard testing indicated that the patients, on average, continued their mental declines during the 2 years after surgery, the pace of cognitive loss was only half as great as the patients had been experiencing before undergoing the gene therapy, says study coauthor Mark H. Tuszynski of the University of California, San Diego in La Jolla. The findings will appear in an upcoming Nature Medicine.

The patients scored best on tests administered more than 6 months after the surgery, suggesting that the transplanted cells took several months to rev up their production of NGF, he says.

This marks the first time that researchers have surgically intervened in Alzheimer's disease to the benefit of patients, Tuszynski says.

Although the gene therapy slows the pace of Alzheimer's decline more than drugs currently prescribed for the disease do, he adds, the surgery is unlikely to represent a cure because it doesn't address the fundamental symptom of Alzheimer's disease: the accumulation of waxy plaques in a person's brain.

"The magnitude of effect shown here is not terribly great, but any positive benefit for Alzheimer's patients would be good," says Curt R. Freed of the University of Colorado School of Medicine in Denver. "This could signal a new phase of treatment for this disorder."

However, Freed notes that skin cells used as a gene-delivery vehicle "may not be as natural to the brain as are the brain's own cells."

With that in mind, Tuszynski is teaming with researchers to inject an innocuous virus, loaded with the gene for NGF, directly into the brains of Alzheimer's patients. The scientists expect this virus to install the gene into neurons, which would then crank out NGF, says David A. Bennett of Rush University Medical Center in Chicago, who is collaborating on the project.
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Title Annotation:This Week
Author:Seppa, N.
Publication:Science News
Date:Apr 30, 2005
Words:499
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