Alzheimer’s disease is a progressive brain disorder in which nerve cells in the brain become damaged, affecting memory, thinking processes, and behavior. The death of cholinergic nerve cells, a specific type of nerve cell in the brain, appears to contribute most to cognitive decline. Thus, current research efforts have focused on methods to prevent cholinergic nerve cell degeneration.

Researchers have identified a substance called nerve growth factor (NGF), which is known to prevent cell death and stimulate cell function. Although NGF is not a newly identified substance, researchers have struggled for some time with how to increase its levels in the brain as a means to prevent cholinergic cell loss.

A new study published in the April 24, 2005 online issue of Nature Medicine describes how researchers sought to genetically modify cells from people with Alzheimer’s so they would produce NGF within the brain. People who had the genetically modified cells injected surgically into their brains showed increased brain activity and up to a 51% reduction in their rate of cognitive decline.

About the Study

Researchers from the University of California, San Diego School of Medicine took skin cells from eight people diagnosed with early Alzheimer's disease and genetically modified them in the lab so they would produce nerve growth factor (NGF). The researchers then performed brain surgery on each person with Alzheimer’s to implant the NGF-producing cells carefully into the damaged areas of the brain. Since the cells were from the subjects’ own skin, there was no risk of the kind of rejection seen when tissues and organs from other donors are transplanted.

The researchers evaluated changes in cognitive function with two tools, the Mini Mental State Examination (MMSE), and the Alzheimer Disease Assessment Scale-Cognitive Subcomponent (ADAS-Cog). The participants also had scans taken of their brain to evaluate brain activity changes.

The Findings

Six of the eight participants completed the study. On average, participants were followed for 22 months, during which time those treated with the NGF-producing cells reduced their rate of cognitive decline by 36% to 51%, depending on the tool used to assess cognitive function. In addition, brain scans showed an increased use of glucose by the brain after the NGF-producing cells were injected, indicating increased brain function.

Researchers also performed an autopsy on the brain tissue of one participant who had died and found new cholinergic cell growth near the site of NGF injection. This finding suggests that cholinergic nerve cell loss—the hallmark of Alzheimer’s—may have been attenuated with gene therapy.

Although these results are promising, there are many limitations to this study. First of all, this is the first study of gene therapy to be conducted in humans with Alzheimer’s and, as such, it involved very few participants—only six who completed the study. There was also no control group of people on conventional Alzheimer’s treatments who could be compared to the patients treated with gene therapy. Thus, for both of these reasons, it is difficult to determine if the promising conclusions of the authors may be due to chance or other reasons, and not due to effective gene therapy.

Another limitation is that many data-gathering practices were modified half way through the study. For example, in the first two participants’ surgeries, the modified cells were injected only on one side of the brain, whereas the remaining six participants had cells injected on both sides.

How Does This Affect You?

This Phase I study is the first, albeit small-scale, attempt to use gene therapy in people with Alzheimer’s disease. Although the results were promising, much more research is needed to prove this therapy safe and effective, and the researchers caution this therapy alone is unlikely to be a cure for Alzheimer’s. It may be several years before a determination can be made as to whether gene therapy will become a viable treatment option for slowing the progression of Alzheimer’s.

Nevertheless, the study is significant for two reasons. First, there are no effective treatments for this devastating disease. Since drug therapy has proved only minimally effective, any new therapeutic strategy is welcome. The positive results of this study suggest that the progression of Alzheimer’s may be slowed.

Second, gene therapy may offer hope for many chronic diseases for which there is no effective cure. This study and others like it are just the beginning of a new field of medicine that will likely begin to bear fruit over the next few decades.