Major Complication of Parkinson’s Therapy Explained

Excerpted from Columbia University Medical Center Newsroom
September 10, 2015

"Researchers have discovered why long-term use of ­­­L-DOPA (levodopa), the most effective treatment for Parkinson’s disease, commonly leads to a movement problem called dyskinesia, a side effect that can be as debilitating as Parkinson’s disease itself.

Using a new method for manipulating neurons in a mouse model of Parkinson’s, a Columbia University Medical Center (CUMC) research team found that dyskinesia arises when striatonigral neurons become less responsive to GABA, an inhibitory neurotransmitter. This suggests that it may be possible to modulate the activity of these neurons to prevent or delay this disabling side effect. The paper was published recently in the online edition of Neuron.

Parkinson’s disease, a progressive neurodegenerative disorder, results from the death of cells in various parts of the brain, especially in a region called the substantia nigra. It is in the substantia nigra that a neurotransmitter called dopamine is formed, and when dopamine is lacking, neurons fire abnormally, impairing one’s ability to control movement.

“While Parkinson’s is not curable, it is treatable with L-DOPA, which is converted into dopamine in ­­­­the brain,” said study leader David L. Sulzer, PhD, a professor of neurobiology in the Departments of Neurology, Psychiatry, and Pharmacology at CUMC and a research scientist at the New York State Psychiatric Institute. “However, while taking L-DOPA helps patients move normally, in many individuals it eventually triggers uncontrolled excessive movements.” Parkinson’s is estimated to affect about one million people in the U.S. and up to 10 million worldwide." [read more]