Researchers Test New Gene Therapy in Alzheimer’s Patient

Doctors at a
University of California-San Diego Medical Center have implanted genetically modified cells into the brain of a 60-year-old Oregon woman with early Alzheimer's disease, hoping to "slow her mental decline," the Washington Post reports. According to lead researcher Mark Tuszynski, an associate professor of neurosciences at UCSD and the Veterans Administration San Diego Healthcare System, the "radical" treatment, which researchers plan to test in seven additional patients, marked the "first trial of gene therapy for a degenerative brain disorder" (Okie, Washington Post, 4/11). Tuszynski said, "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," but added, "It's unlikely to be a cure" (AP/Las Vegas Sun, 4/10). Researchers removed the cells from the woman's skin and "equipped" them with a gene to "produce nerve growth factor," a substance that promotes the "growth and survival" of brain cells (Washington Post, 4/11). Dr. William Mobley, chair of the neurology department at Stanford University, called the procedure a "very important first step" in Alzheimer's treatment (Blakeslee, New York Times, 4/11). However, some experts "expressed concern" that with "no simple way" to remove the genetically modified cells, called fibroblasts, or "stop their action" in the brain, complications "may be difficult" to treat. "It's quite aggressive," Vassilis Koliatsos, an associate professor of pathology and neurology at Johns Hopkins School of Medicine, said, adding, "Growth factors are extremely powerful compounds, and they're not selective for a particular brain system. ... We've got to be watching here."

The pilot study of gene therapy in Alzheimer's patients was approved in 1999 by the FDA and the NIH's Recombinant DNA Advisory Committee. The agencies based their decision on years of research in animals that "showed nerve growth factor could enhance survival and function of cholinergic nerve cells after surgery or the partial degeneration associated with aging," Tuszynski said. Although Tuszynski predicted that patients would not suffer side effects from the experiment because they are receiving lower doses than previously studied, researchers have warned study participants that they may experience bleeding, tumors, chronic pain and weight loss (Washington Post, 4/11). Bill Thies, vice president of medical and scientific affairs for the Chicago-based Alzheimer's Association, said that he remains "cautious but optimistic" about the research. Thies said, "Anytime you start a clinical trial, you don't know whether the benefits outweigh the risks. You always want to be cautious at the beginning." He also pointed out that the "complexity" of the procedure may "hamper wider use," concluding, "We're not going to do neurosurgery on four million people" (AP/Las Vegas Sun, 4/11). Tuszynski used a modified virus, removing the "disease-causing genes," as a carrier to insert the nerve growth factor gene. According to the Washington Post, he co-founded Ceregene Inc., a San Diego company -- now owned by Cell Genesys Inc. -- that controls the patent rights to the technology used to synthesize the modified cells (Washington Post, 4/11).