In the first-ever gene therapy application of its kind in humans, researchers have successfully slowed cognitive decline in patients suffering from Alzheimer's disease. Although the technique is unlikely to cure the disease, experts say it could be combined with other therapies to substantially slow the advance of Alzheimer's.
Neurodegenerative diseases such as Alzheimer's are generally marked by a loss of brain synapses and neurons, in particular cholinergic neurons. These neurons conduct impulses outwards from the brain or spinal cord by releasing neurotransmitters such as acetylcholine and dopamine. Over time, the loss of such neurons and their junctions damages a person's mental abilities. One way to halt the decline of these neurons is to treat the brain with nerve growth factor (NGF), a protein that prevents nerve cells from dying and stimulates their function. But administering NGF is risky: It can stimulate other neurons, causing pain and weight loss. So NGF must be delivered to the exact place where neurons are failing.
Neurobiologist Mark Tuszynski of the University of California, San Diego, and colleagues decided to deliver NGF using gene therapy, as the treatment was earlier found to be safe and effective in primates. They injected connective skin tissue cells, genetically modified to produce and secrete NGF, deep into the brain of eight patients aged 50 to 80 with mild Alzheimer's. Twenty-two months after treatment, the patients experienced an average decline of about 3 points on standardized mental status tests versus a decline of about 6 points a year before treatment.
What's more, brain scans of the patients 6 to 8 months after treatment showed an increase in the brain's uptake of glucose, a sign of increased mental activity, the researchers report 24 April in Nature Medicine. Examination of the injection site in a patient who died a few weeks after the treatment also revealed potent growth of the bulbous ends of nerve cells where neurotransmitters are stored. "This is the first evidence in humans that degenerating neurons respond to NGF," says Tuszynski.
And it sets a bit of a record. "The use of NGF gene therapy resulted in greater benefits than any other treatment used to date," says Huntington Potter, a neuroscientist with the University of South Florida in Tampa. "The study provides hope that other, less invasive methods for stimulating existing cholinergic neurons may be equally beneficial and more easily administered." But Potter cautions that the new technique will be costly to apply to a large number of patients and much work still needs to be done on what causes the disease in the first place.