By LEE BOWMAN
Scripps Howard News Service
April 24, 2005
Researchers at the University of California-San Diego said mental-status tests showed that the rate of cognitive decline had been reduced between 36 percent and 51 percent in the patients, who were all in the early stages of the disease.
By comparison, the best reductions in rate of decline for patients taking drugs for Alzheimer's are 6 percent, with an average duration of three to six months.
The disease is common in aging, affecting about 4.5 million Americans. Unless there are significant advances in treatment, expects predict there will be nearly 18 million Americans with the disease by 2050.
"If validated in further clinical trials, this would represent a substantially more effective therapy than current treatments for Alzheimer's disease," said Dr. Mark Tuszynski, the principal investigator for the study and a professor of neuroscience at UCSD. He is also a neurologist with the VA San Diego Healthcare System.
The study was published online by the journal Nature Medicine.
"This would also mark the first therapy for a human neurological disease that acts by preventing cell death," Tuszynski added.
Brain-imaging studies also found an increase in the use of glucose in the brains of the treated patients compared with patients at the same stage who had not been treated.
In addition, researchers examined the brain tissue of one study participant who died of a heart attack five weeks after getting the injections and found robust growth of extensions from brain cells around the area where growth factor was inserted.
Higher brain regions that are the center of language, memory and other functions are regulated by a chemical substance called acetylcholine that is produced from a small clump of cells located below the frontal lobe of the brain. Cells from around the brain send nerve-growth factor to the acetylcholine center, called the nucleus basalis, telling it to make more.
As brain cells in those higher brain regions are killed in Alzheimer's patients, the production center for acetylcholine doesn't get the signals it needs to keep memory, attention and reasoning functions active.
Other studies have shown that the loss of the chemical messenger cells matches the severity of dementia, the pace of loss of nerve-cell connections and the growth of plaque deposits that damage cells in the brains of Alzheimer's patients.
The gene therapy is designed to fix this problem by injecting a large source of nerve-growth factor right into the nucleus basalis.
The San Diego researchers gave the injections to eight patients starting in April 2001. Cells from the patients' skin were genetically modified to produce nerve-growth factor. Those cells were cultured in labs and several million of them were then implanted deep within the brain in operations that lasted up to 11 hours.
The procedures were primarily done to test the safety and toxicity of the implants. It was the first attempt in humans to expand on years of successful experiments Tuszynski and colleagues had done on monkeys suffering from atrophied brain cells.
Injections were first done with the patients awake but lightly sedated. However, two patients moved as the injections were being done, causing bleeding in the brain. One of those patients was the heart-attack victim.
So surgeons on the team changed their approach, putting the remaining six patients under general anesthesia, and there were no further complications. Cognitive outcomes were measured in those patients at the time of treatment and every few months afterward.
Another round of studies of nerve-growth factor in Alzheimer's patients, using a different delivery agent, is under way at Rush University Medical Center in Chicago.
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