Scientists at Jefferson Medical College have used gene therapy to reverse the progression of Parkinson's disease in rats. They have found that by adding a gene for an enzyme, they were able to reprogram brain circuitry and halt the deterioration of dopamine producing brain cells, one of the key problems in the disease.

"It's not just inserting a replacement for a missing or mutated gene as a treatment for a genetic disorder," says Michael Oshinsky, Ph.D., research assistant professor of neurology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and part of the team reporting its results October 11 in the journal Science. "This is more profound. We are actually changing the brain's circuitry as treatment for a disease."

According to Dr. Oshinsky and Jia Luo, M.D., research associate at Jefferson Medical College of Thomas Jefferson University, in Parkinson's, a portion of the brain called the subthalamic nucleus is overactive. These cells produce glutamate, an excitatory neurotransmitter, or chemical message carrier, into another region called the substantia nigra, which is important for the coordination of movement and where the brain chemical dopamine is made. Parkinson's is caused by the deterioration of dopamine-producing nerve cells.

The researchers - including scientists from Jefferson, the University of Auckland, New Zealand, and Cornell University - took their cues from work with deep brain stimulation, where brain cells in the subthalamic nucleus are stimulated at a high frequency as a treatment for late-stage Parkinson's. This treatment prevents overactivity in the substantia nigra.

The team, led by Matthew During, M.D., formerly of Jefferson Medical College of Thomas Jefferson University and now at the University of Auckland, decided that instead of turning off the neurons in the subthalamic nucleus, they would attempt to change the neurons from excitatory to inhibitory, which would then contain the inhibi
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Contact: Steve Benowitz
steven.benowitz@mail.tju.edu
215-955-5291
Thomas Jefferson University
10-Oct-2002

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