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Mice With Parkinsonís Gene May Help Scientists Test New Therapies

Scientists at Columbia University and Weill Medical College of Cornell University have successfully developed a new animal model for Parkinson’s disease (PD) – a valuable tool for testing new Parkinson’s therapies and studying the underlying causes of the disease.  The report, led by Chenjian Li, Ph.D.,  and M. Flint Beal, M.D., at Weill Medical College and Robert Burke, M.D., and Tinmarla Francis Oo at Columbia University, was published in the June 7 edition of Nature Neuroscience.

For scientists to develop new treatments for people with Parkinson’s, it is essential to first test them in animals.  Progress in Parkinson’s has been hampered to date because scientists have not had an animal model that accurately mimics the progression of PD in humans.

The scientists in this study have engineered a strain of mice whose DNA contains the gene most commonly linked to Parkinson’s disease.  The mouse strain carries a complete human LRRK2 gene with a mutation that causes PD in an autosomal dominant fashion — in other words, a mouse that inherits a copy of the gene from one parent will develop disease. These mice are the first animal models to develop both brain changes and motor symptoms similar to human PD.

The researchers cite several points of similarity between the disease that developed in the mice and Parkinson’s in humans. For instance, the mice with the LRRK2 mutation grew normally, but their movements slowed progressively as they got older. By the age of 10 to 12 months — middle age for a mouse — they were almost immobile.  Treating the mice with levodopa, the first-line therapy for PD, restored their ability to move.  The scientists also observed changes in brain chemistry and in brain cells in the mice that were similar to those seen in people with PD.  For example, like people living with the disease, the dopamine releasing neurons in the brain of the mice showed progressive signs of deterioration. 

Despite the similarities, the mouse model does not fully replicate human PD as the mice do not generate Lewy bodies — the clumps of alpha-synuclein observed in human PD. 

Nevertheless, these parallels make it possible for scientists to study, in the mice, how Parkinson’s develops over time and to investigate therapies that could slow or prevent the progression of disease.  According to Dr. Burke, “This mouse model will, for the first time, allow scientists to observe the progressive nature of Parkinson’s disease in a model system where sophisticated tools can be used to understand how and why PD begins and then how it can be treated effectively.”

The Parkinson’s Disease Foundation partially funded this work.


Source Date: Jun 10 2009