Development of new mouse model of Parkinson's may lead to new treatments

Past attempts to create a mouse model for Parkinson's disease capable of reproducing the movement impairments and degenerative brain changes associated with the human form of the disease have failed, due to technological limitations. Now for the first time, scientists at Weill Cornell Medical College have successfully taken advantage of a new transgenesis technology called BAC (bacterial artificial chromosome) to create a mouse model of Parkinson's. By using the BAC technology to insert large DNA fragments into the genome, senior author Dr. Chenjian Li, assistant professor of neurology at Weill Cornell Medical College, and his colleagues were able to successfully introduce a mutant form of the LRRK2 gene -- the most common genetic cause of Parkinson's - into the mouse's genome.

The researchers report that they observed the same slow movements associated with Parkinson's in the mice expressing the mutant gene. And when they treated the mice with levodopa, the same drug used with Parkinson's patients, the mice gained back normal movements. The team conducted additional research demonstrating that those same mice also had impaired release of the brain neurotransmitter dopamine, just as it occurs in the human disease. Their study further led them to discover that "the dopamine deficit came from disintegration, not of the dopamine neurons themselves, but of their axons, the long, filament-like structures responsible for transmitting dopamine to distant targets in the brain." The ability to understand the disease at a deeper level may lead to improved treatment, and possible a cure, for Parkinson's disease, suggests Dr. Li.

"The new model will provide scientists with an appropriate stage on which to screen for effective medications," explains Dr. Li. "It will also show us the disease in real time, allowing us to track its progression at a cellular and molecular level. What we learn will then feed back into the drug development process. From a longer-term perspective, this also gives us a picture window into normal biology. The new mouse model will provide an opportunity to investigate the brain's dopaminergic system, a brain circuit critical to movement, emotions and drug addition," he says.

News Release: Mice with Parkinson's disease gene may point the way to new treatments www.healthnewsdigest.com  June 8, 2009