April 10, 2001 -- Doctors at the University of California, San Diego, are testing a new genetic therapy they hope will help slow the degeneration of the brain caused by Alzheimer's disease.
As part of the first phase of an experimental gene therapy trial, researchers removed skin cells from a 60-year-old Oregon woman in the early stages of the progressive brain disease. They genetically engineered the cells to secrete a protein called nerve growth factor, which is usually produced in healthy brains to maintain nerve connections in the brain. Last Thursday, doctors surgically implanted the experimental material into her brain.
The woman, who has requested to remain anonymous, tolerated the procedure well. In fact, she remained conscious during the entire procedure and was able to converse with her surgeon, Dr. Hoi Sang U, after the procedure. She was discharged from the hospital two days later.
The 11-hour procedure marked the first use of human gene therapy in the treatment of brain disease, researchers said Monday.
If the therapy proves to be successful, doctors say the procedure could eventually be done on an outpatient basis.
"Our hope is that this procedure will be a way of delaying the progress of the disease and improving the quality of life for several years," says Mark Tuszynski, MD, PhD, who developed the therapy. "It's unlikely to be a cure."
Another patient will undergo the procedure in three months and researchers are seeking six more candidates.
Hopefully the implanted cells will begin to improve brain function over the next few weeks, but doctors caution that it will take years to determine whether this procedure is a useful and safe therapy for the general public. Then future tests will be needed to gauge whether patients maintain their mental abilities.
Last year, WebMD reported on Tuszynski's presentation of his gene therapy concept at the 52nd Annual Meeting of the American Academy of Neurology. That stage of the research was based on work performed on the brains of aging rhesus monkeys.
His results were so promising that he submitted a proposal to the FDA to get permission to test the technique on humans. He received authorization and began to recruit patients.
Alzheimer's disease and aging are not the same process. But there are similarities in both, such as a decline in memory and thinking ability. And as one ages, the risk of developing Alzheimer's increases.
Monkeys do not get Alzheimer's. However, Tuszynski found similarities between what happens to an aging monkey's brain and how Alzheimer's disease affects the human brain. In both cases, specialized nerve cells deep in the brain deteriorate over time.
In his experiments, Tuszynski and colleagues injected five monkeys with skin cells genetically modified to produce nerve growth factor. It was found to nourish the nerves and help maintain the networks responsible for thought and memory -- regions which suffer heavy damage when a human develops Alzheimer's.
Last year, when the California team made its presentation, observers told WebMD they were hopeful but noted they still did not know if the nerve cells damaged by Alzheimer's were already dead or if they were just shriveled and could be revived.
"If they're dead, it may be too late," said Michael E. Selzer, MD, professor of neurobiology at the University of Pennsylvania. "But if many of them are in the process of dying and they are dependent on nerve growth factor for robust survival, then it may still be that this sort of gene therapy will have a beneficial effect."
Bill Thies, vice president of medical and scientific affairs for the Chicago-based Alzheimer's Association, is cautiously optimistic about the new procedure.
"Anytime you start a clinical trial, you don't know whether the benefits outweigh the risks," says Thies. "You always want to be cautious at the beginning."
He notes that Alzheimer's only afflicts humans, and doctors may not experience the same successes with humans that they had with monkeys. He also says the complexity of the procedure may be a downside.
"We're not going to do neurosurgery on four million people," says Thies.