Gene Therapy Shows Promise Against Alzheimer’s

May 1, 2005

May 1, 2005

Results from a small pilot study suggest that gene therapy, a novel approach to the treatment of Alzheimer’s and other diseases for which effective treatments are lacking, may help to slow mental decline for those with the devastating brain ailment.

Scientists at the University of California, San Diego tested the approach on eight people in the early stages of Alzheimer’s disease. Tests of memory and thinking skills were given before and after the procedure. Those who received the treatment had less mental decline in the 22 months following the treatment than in the 14 months before.

The study is the first to test gene therapy in Alzheimer’s disease. The technique has been tried in people with Parkinson’s disease and other ailments, so far with little success. Side effects have been serious, even fatal, in some people who undergo testing.

In the current study, skin cells were taken from the back, then mixed with DNA in a laboratory so that the cells carried a gene that produces a substance called nerve growth factor. Nerve growth factor, or NGF, boosts connections between nerve cells, including those responsible for memory and learning. The genetically altered skin cells were then injected into the brain.

What the Study Showed

The NGF-secreting skin cells appear to stimulate the growth of brain cells that produce the substance acetylcholine, a chemical that boosts communication between nerve cells and is vital for memory. People who received the treatment showed less decline on memory tests compared to their rates of decline measured before the surgery.

Over the study’s follow-up period of 22 months, the rate of cognitive decline was reduced by as much as 51 percent, the researchers said. When the rate of decline was measured from 6 to 18 months after surgery, a period after which brain cells had a chance to grow, the six patients who remained in the study either improved or remained stable, with only one showing some mental decline.

“By comparison, currently approved medications for Alzheimer disease have an estimated impact on these cognitive measures of 5 percent, and are not known to affect decline over prolonged periods,” the researchers wrote. New connections also formed between brain cells involved in memory, and there was greater activity in areas of the brain affected by Alzheimer’s disease.

“If these effects are borne out in larger, controlled trials, this could be a significant advance over existing therapies for Alzheimer’s disease,” said study leader Mark H. Tuszynski, director of the University of California, San Diego’s Center for Neural Repair.

A Difficult Surgery

Experts caution that gene therapy is still highly experimental, and that the number of patients tested was small. Much larger trials will be needed to assess whether the treatment is really effective and safe, and it could be years before practical treatments are widely available. Many earlier gene therapies that looked promising in early trials turned out to be unsafe and/or ineffective in later trials.

Because NGF is too large a molecule to pass directly from the bloodstream into the brain, treatments using the substance cannot be given via pills or by injections into the bloodstream or muscles. Other studies showed that when NGF was injected directly into the brain, it resulted in severe side effects. In contrast, implantation of NGF-producing cells into a specific brain region (as was done in this study) controlled the effects of NGF by restricting its distribution in the brain.

The operation currently involves injecting altered cells directly into the brain so the cells seed brain areas controlling memory and secrete NGF. The first two patients underwent the surgery under local anesthesia, in which they were sedated but aware. Both moved their heads during the operation, which resulted in brain hemorrhaging, and one of the patients died. The remaining six patients had the procedure done under general anesthesia, with the head prevented from moving, and it appeared to be safe.

Doctors are hoping to develop more efficient means of delivering NGF to the brain. In one new study under way at Rush University School of Medicine in Chicago, doctors are injecting viruses, genetically modified to hold a gene for NGF, into the brains of 12 people with Alzheimer’s in the hopes that the altered viruses will program brain cells to produce their own NGF.

Gene therapy is not likely to be a cure for Alzheimer’s. Results of this small study, however, the first gene therapy experiment in people with Alzheimer’s, are promising. The results suggest this or a related treatment may open up new areas of investigation in halting Alzheimer’s disease, which affects some 4.5 million Americans today.

The Fisher Center for Alzheimer’s Research Foundation funds research initiatives critical for finding new approaches to the treatment and cure of Alzheimer’s disease. To learn more, visit www.ALZinfo.org.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Mark H Tuszynski1, Leon Thal, Mary Pay, et al: “A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease.” Nature Medicine, Online edition, April 24, 2005.


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