A team of U.S. scientists has used gene therapy to slow neural degradation in rats that have an affliction resembling Parkinson's disease. The work, published in tomorrow's issue of Science,* holds out hope that gene therapy will be useful for limiting the severity of Parkinson's, a progressive disease that afflicts about 500,000 people in the United States alone.
Parkinson's disease is caused by the death of neurons in the brain that produce dopamine, a chemical that shuttles signals between neurons and is responsible for controlling the body's movement. Scientists have long known that a bath of protective proteins in the brain, known as neurotrophic factors, can help curb the progression of Parkinson's disease by keeping those dopamine-producing neurons healthy. Currently, clinical trials are under way to test the effectiveness of mechanically pumping large amounts of these proteins into the affected area of patients' brains on a continuing basis.
Some researchers have been trying an alternative route: engineering gene-delivery vehicles such as viruses to transfer neurotrophic-factor genes directly into brain cells. The hope is that these cells would then manufacture the protective protein on their own. In one such approach, researchers surgically remove brain cells, use viruses to transfer genes to the cells, and then graft them back into the animal's brain tissue.
Now, a team from the University of Rochester in New York, led by neurobiologist Martha C. Bohn, reports promising results using a less invasive scheme: The researchers injected engineered viruses directly into the afflicted brain tissue of rats. They started by genetically engineering a nonreplicating form of the common cold virus, called adenovirus, to carry the gene for a protein called glial cell line-derived neurotrophic factor, or GDNF. They then induced Parkinson's symptoms in laboratory rats by killing the rodents' dopamine-producing neurons with toxins, and injected the viruses into the damaged tissue of some of the animals. The brain cells of the treated rats began secreting GDNF on their own. Six weeks later, 69% of the neurons in untreated rats had died, compared with 21% of the neurons in rats injected with the viral vector.
The researchers caution, however, that it's not yet clear how closely the toxin-induced neural damage in rats mimics the state of diseased neurons in Parkinson's, especially because the mechanism that leads to such damage in humans remains unknown. Nevertheless, "[the] study is very important because it demonstrates for the first time that we can use gene therapy to transform cells in the brain into ones that will secrete GDNF," says Jeffrey Kordower, a professor of neurological sciences at Rush Presbyterian Medical Center in Chicago.