March 25, 2003
Controlling Neurons May Ease Parkinson’s Disease
CHICAGO— Blocking or eliminating a specific potassium channel in a small group of brain cells may improve or prevent the symptoms of Parkinson’s disease, a debilitating and progressive neurodegenerative disease that afflicts more than 1 million people in the United States.
In Parkinson’s disease, neurons that release dopamine die. The loss of dopamine causes an array of debilitating symptoms that include resting tremor, muscle rigidity, and slowed movement.
Although the cause of the disease remains uncertain, D. James Surmeier, PhD, and colleagues at Northwestern University’s Feinberg School of Medicine have discovered a way of potentially lessening the symptoms and progression of the disease. The investigators describe their findings in the March issue of Nature Neuroscience .
Dr. Surmeier, who is Nathan Smith Davis Professor and chair of physiology at the medical school, and his co-researchers found that the “bad” behavior of neurons responsible for the symptoms of Parkinson’s disease is controlled by a potassium channel that is found almost exclusively in the affected brain regions.
This potassium channel—referred to as Kv3.4—is found in only small subsets of neurons outside the basal ganglia. Neurons of the subthalamic nucleus are enriched in this channel, making them capable of the “bad” activity patterns found in Parkinson’s disease patients.
Surgically destroying these neurons or inserting a stimulating electrode in the brain to disrupt the neurons’ “bad” activity provides symptomatic relief in late-stage Parkinson’s patients. Unfortunately, these strategies can cause unwanted side effects, including uncontrolled movement.
“The perfect therapy for Parkinson’s disease would be to prevent neurons from exhibiting the behavior that causes the symptoms of the disease without altering their ‘good’ behaviors,” Dr. Surmeier said.
“Current strategies don’t distinguish between these two modes of activity. It is also possible that the ‘bad’ behavior of these neurons contributes to the progression of the disease, which may not be ameliorated by deep-brain stimulation strategies that are being used today,” he said.
The findings from his group’s current study suggest that it is possible to stop high-frequency spiking in these neurons by blocking potassium channels with the Kv3.4 subunit or by eliminating the subunit using gene therapy techniques.
“Doing so will eliminate the ‘bad’ behavior but, importantly, preserve the ‘good’ behavior—normal regular spiking—of these neurons,” he said.
Dr. Surmeier also said that it is possible the high-frequency burst of spikes in subthalamic neurons is responsible for Parkinson’s disease itself, so that correcting this behavior will stop the disease in its tracks—the focus of his group’s ongoing research at the Feinberg School.
The study was funded by a grant from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health. Dr. Surmeier received a Jacob Javits Neuroscience Investigator Award from the NINDS to pursue this research.
