By injecting a gene hitched to a virus into the brains of monkeys, scientists have alleviated symptoms of Parkinson's disease in the animals. The experiment, reported in the 27 October issue of Science, marks the first successful use of this gene therapy technique in primates; scientists say it holds promise for arresting Parkinson's disease and similar disorders in humans.
Parkinson's disease, which affects about 1 million Americans, destroys dopamine-producing neurons in the brain. As dopamine levels fall, the disease's characteristic symptoms appear: tremors, rigidity, and difficulty in initiating motion. In the early 1990s scientists discovered that GDNF, a protein produced in embryonic brain stems and other nervous system tissue, strongly stimulates the growth of dopamine neurons. Since then, two groups of researchers have successfully alleviated Parkinson's-like symptoms in rats by using viruses to carry GDNF genes into the animals' brains. Encouraged by this work, a team of scientists led by Jeffrey Kordower, a neuroscientist at Rush Presbyterian-St. Luke's Medical Center in Chicago, took the next step: introducing the GDNF genes into rhesus monkeys.
Kordower's team spliced human GDNF genes to a lentivirus, which readily enters nerve cells. They then injected the virus into three dopamine-deprived areas in the brains of two groups of monkeys: eight elderly animals with age-related brain deterioration and 10 animals with Parkinson's-like symptoms induced by a toxin. One to 2 months later, dopamine activity in the GDNF-treated monkeys of both groups was nearly double that of similar-sized control groups. Treated monkeys were also trouncing control animals in coordination task tests. Although the trial ended after 3 months, other monkeys in Kordower's lab continue to exhibit elevated dopamine activity 8 months after GDNF gene treatment.
Scientists praise Kordower's meticulous work, but some caution that the human response to GDNF can't be predicted based on animal trials. "This may be the magic bullet," says Ole Isacson, director of neuroscience research at McLean Hospital at Harvard Medical School. But a counterscenario in which GDNF elicits an acute toxic reaction in Parkinson's patients is equally likely, says Isacson. (To head off that problem, Kordower is currently studying how the expression of the GDNF gene can be turned off should it have unwanted side effects--a prerequisite for human trials.)
Others have fewer reservations. Because therapy has worked across two species and several kinds of brain damage, it will likely work in humans, too, says Ron Mandel, a neuroscientist at the University of Florida, Gainesville. "This is where gene therapy shines," he says. "This relatively noninvasive procedure needs to be applied only once. And then it's always there as needed."