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A Better Shot at Treating Parkinson's
4 August 1997 7:00 pm
A gene-therapy technique can help protect rats against brain damage similar to that of Parkinson's disease. In tomorrow's Proceedings of the National Academy of Sciences, French researchers report that a single injection of a genetically engineered virus into rats protects the same brain cells that die off in the neurodegenerative disease. A similar therapy may eventually help treat Parkinson's disease in humans.
The tremors and paralysis of Parkinson's begin with the death of cells that produce the neurotransmitter dopamine. No one knows what kills the cells, located primarily in a part of the brain called the substantia nigra, but previous work in animals has shown that a protein called glial-cell-line-derived neurotrophic factor (GDNF) can protect dopamine-producing neurons. Although preliminary human trials are under way, the therapy requires multiple injections into the brain--an invasive and dangerous undertaking. Several teams have been trying to develop a one-time injection of a virus that defends brain cells by adding the GDNF gene, with some initial success. When injected into the substantia nigra, the modified virus can keep the dopamine-producing neurons alive in rats suffering from Parkinson's-like symptoms (ScienceNOW, 6 February). Trouble is, the substantia nigra is buried deep in the brain and is difficult to reach.
Now, neurobiologists Jacques Mallet and Philippe Horellou of the National Center for Scientific Research in Paris and their colleagues have slipped around this obstacle: When they inject the virus into a more accessible brain region, called the striatum, cells in the substantia nigra take it up as well. In addition, when they administered the virus to rats and then treated them with a chemical that kills dopamine-producing cells, the therapy not only reduced the nerve cell loss caused by the chemical, but it also decreased some of the resulting motor damage.
The work could make an eventual human treatment more feasible, says neurobiologist Martha Bohn of Northwestern University in Evanston, Illinois, who is working to develop a similar therapy. "It's an excellent proof of principle," she says. But she cautions that trials in primates have just begun, and several hurdles remain. No one knows if the virus will be safe or effective in humans, she says, and it may be more difficult to deliver it in large primate brains.