Gene Therapy for Alzheimer's

For many people, more disturbing than the idea that the body will decline with aging is the notion that their mind will go. Perhaps no one feels the weight of this grim outlook more than individuals diagnosed with Alzheimer's disease. Results of a study described today in the Proceedings of the National Academy of Sciences, however, may offer new hope. Building on earlier research aimed at reversing age-related changes in the brain, scientists using gene therapy have succeeded in restoring axonsthe all-important fibers that carry messages to and from cells in the brainin aged monkeys. According to team member Mark Tuszynski of the University of California at San Diego, the new findings provide further support for human clinical trials of the treatment.

Previous work had shown that surgically transplanting cells genetically altered to produce nerve growth factor (NGF) into the brains of rhesus monkeys returned their neuron cells40 percent of which had atrophied as a result of normal agingback to normal levels within three months. The new study shows that the same treatment also restores the axons that connect these neurons within the brain. "Following gene therapy, the axons were restored to levels seen in young monkeys, and sometimes exceeded those levels," team member James Conner notes. The images at the right illustrate the normal density of axons in a young individual (top), that of an aged individual (middle) and that of an aged individual who received the NGF treatment (bottom). Importantly, the findings also put to rest concerns some researchers had that axons might grow toward the implant, rather than out into the cortex, where intellectual processing occurs.

Currently two Alzheimer's patients are enrolled in a phase 1 clinical trial of the treatment now under way, and the scientists are looking for six more participants. "If we see a fraction of the effects in humans that we see in primates," Tuszynski remarks, "we may have something here."