Safer Electrical Therapy for Parkinson's

Delivering electrical stimulation via the spinal cord could help ease symptoms of the disease.

Delivering electrical stimulation to the spinal cord through tiny, platinum electrodes could ease the severe motor deficits of Parkinson's disease as effectively as a much more intrusive procedure currently in clinical use, according to a new study in rodents. If the findings are confirmed in humans, scientists say, the procedure could dramatically improve treatment for the disease by making electrical therapies safer and more broadly available.

Stimulating the brain: Neural activity in the brain of a Parkinsonian rat before (top) and after (bottom) electrical stimulation is applied to its spinal cord. The stimulus elicited a flood of excitatory (red) and inhibitory (blue) neural responses. Credit: Romulo Fuentes

Parkinson's is a neurodegenerative disorder that develops when the brain cells that produce, excrete, and reabsorb a neurotransmitter called dopamine mysteriously begin to die. Patients initially develop muscle tremors; in the later stages of the disease, their limbs go rigid, and their movements slow to a painful crawl. The disease can be treated by replacing dopamine with a drug called levodopa, or L-dopa, but the drug loses its effectiveness over time. When drugs fail, patients often turn to an invasive surgical treatment called deep brain stimulation, which uses an electric pacemaker to send pulses to very specific areas of the brain. Thousands of Parkinson's patients have received the brain implants to date.

Researchers at Duke University accidently came upon the idea of stimulating the spinal cord as a possible treatment for Parkinson's. While examining rats engineered to exhibit symptoms characteristic of Parkinson's, they noticed that groups of neurons in two areas of the brain, the cortex and the basal ganglia, were firing synchronously. The rhythmic activity was reminiscent of the mild, continuous seizures seen in patients with epilepsy. "I had seen this a decade ago," says Miguel Nicolelis, a professor of neurobiology and codirector of the Center for Neuroengineering at Duke University. At the time, Nicolelis and his collaborators were searching for ways to disrupt rhythmic seizures by stimulating peripheral nerves.

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Nicolelis reasoned that a similar approach might work for Parkinson's. So he and his student Romulo Fuentes took their dopamine-depleted mice and rats and attached tiny platinum electrodes to the base of their spinal cords. "When we stimulated them with a small current, we got an effect that was identical--and even better--than what people get when they do this deep brain stimulation," Nicolelis says. The Parkinsonian animals' slow stiff movements were replaced with healthy mouse and rat behaviors.

When Nicolelis and Fuentes combined the electrical stimulation with L-dopa, the effects were even more startling. The electric pulses, combined with only 20 percent of the typical drug dose, resulted in a long-term effect that mimicked L-dopa therapy without appearing to replicate the drug resistance that normally builds up over time. The research was published yesterday in the journal Science.