Mouse model opens window into Parkinson’s

CORNELL (US)—A new mouse model of Parkinson’s disease promises to be a boon to research, both in terms of basic science and drug development, scientists at Weill Cornell Medical College predict.

M. Flint Beal, a professor of neurology and neuroscience, says the lack of a “truly workable animal model of the human disease” has been a major roadblock to developing therapies to prevent progression of Parkinson’s.

“This new model will now address this critical need,” adds Beal, coauthor of a study published in the June 7 issue of the journal Nature Neuroscience.

Using a new technology called bacterial artificial chromosome, senior author Chenjian Li, assistant professor of neurology at Weill, and his colleagues introduced a mutant form of the LRRK2 gene—the most common genetic cause of Parkinson’s—into the mouse genome.

Mice with the mutant gene had slowed movement as they aged, similar to humans, and were able to move normally when treated with levodopa, a drug commonly used to treat human patients.

Research by Robert Burke, the Alfred and Minnie Bressler Professor of Neurology at Columbia University Medical Center, showed mice with impaired movement also had impaired release of dopamine, just as it occurs in the human disease.

The deficit was not from disintegration of the dopamine neurons themselves, Burke found, but of their axons, the long, filament-like structures responsible for transmitting dopamine to targets in the brain.

The two standard types of treatment—medication and surgery—do not stop the disease’s progression, Li says.

“The new model will provide scientists with an appropriate ‘stage’ on which to screen for effective medications,” adds 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, the new mouse model will give scientists “a picture-window into normal biology,” Li says, and will “provide an opportunity to investigate the brain’s dopaminergic system, a brain circuit critical to movement, emotion, and drug addiction.”

Columbia University Medical Center and the Bedford VA Medical Center contributed to the study, which was supported by the National Institute of Neurologic Disorders and Stroke, the Michael J. Fox Foundation, and the Parkinson’s Disease Foundation.

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