Researchers in the US found that when they electrically stimulated the spinal cord of mice and rats that had depleted levels of dopamine, the chemical that is lacking in the brains of people with Parkinson’s, their slow, stiff movements were replaced with the behaviours of healthy animals. They hope one day to offer the same benefits to Parkinson’s patients by developing a small spinal cord stimulator that is implanted under the skin.

The study was the work of senior study investigator Dr Miguel Nicolelis, the Anne W Deane Professor of Neuroscience at Duke University Medical Center in Durham, North Carolina, and colleagues, and is published in the 20 March issue of the journal Science.

Nicolelis and colleagues developed a prosthetic device that delivers electrical stimulation to the dorsal column in the spinal cord and attached it to the surface of the spinal cord in mice and rats.

A press statement from Duke University describes the new method as the first potential therapy to target the spinal cord instead of the brain.

If proven in humans, it offers a less invasive approach for treating Parkinson’s disease compared to other alternatives to medication such as deep brain stimulation. It also has potential for “widespread use in conjunction with medications typically used to treat Parkinson’s disease”, said Nicolelis.

The spinal cord is the main route through which the nerves of the body send sensory signals to the brain and through which the brain sends motor signals to the body.

When the researchers turned the device on, the stiff and slow movements of the rats and mice were replaced with behaviours of healthy animals within 3.5 seconds of receiving electrical stimulation.

Nicolelis said they saw “an almost immediate and dramatic change in the animal’s ability to function when the device stimulates the spinal cord”.

The researchers tested the device using different levels of electrical stimulation on mice and rats with acute and chronic dopamine deficiency. They also used it in combination with different doses of a dopamine replacement drug called L-DOPA (3,4-dihydroxy-L-phenylalanine).

They found that when used on mice and rats on its own (ie no L-DOPA), the electrical stimulation led to them being 26 times more active. With only two doses of L-DOPA, the electrical stimulation produced movement comparable to five doses of the drug alone.

Lead author and postdoctoral fellow at Duke University, Dr Romulo Fuentes explained the importance of the finding:

“This work addresses an important need because people living with Parkinson’s disease face a difficult reality — L-Dopa will eventually stop managing the symptoms.”

“Patients are left with few options for treatment, including electrical stimulation of the brain, which is appropriate for only a subset of patients,” he added.

Nicolelis had the idea for the device when he experienced a “sudden moment of insight” while analyzing the brain activity of mice with Parkinson’s and realized it was similar to what he had seen while studying epilepsy a decade earlier. “The ideas began to flow from there,” he said.

The brain activity of animals with Parkinson’s has a rhythm similar to the low frequency continuous seizures in epilepsy, a condition that is sometimes treated by electrically stimulating the peripheral nerves to improve communication between the spinal cord and the body. So Nicolelis and colleagues wondred what would happen if they applied this idea to a Parkinson’s disease model.

Study co-author Per Petersson said that:

“Our device works as an interface with the brain to produce a neural state permissive for locomotion, facilitating immediate and dramatic recovery of movement.”

“Following stimulation, the neurons desynchronize, similar to the firing pattern that you would see when a healthy mouse is continuously moving,” he added.

In a healthy body, neurons, the brain and spinal cord cells that transmit sensory and motor signals between the brain and body, fire at certain rates, sending a sort of Morse code to the nerves that control the muscles to produce the right kind of movements. This signalling pattern breaks down in people with Parkinson’s.

The low frequency oscillations or seizures in rats and mice with Parkinson’s are similar to those seen in humans with the disease, and the researchers suggest that it is these that impair motor function, so reducing them with electrical stimulation is what restores the motor function.

The researchers anticipate that once the device is proven to be safe and effective in further research and human trials, it will be similar to those already used to treat chronic pain, where small leads are implanted over the spinal cord and connected to a portable generator. During the trial period the generator is external, but a permanently fitted one could be implanted under the skin, said Nicolelis.

“If we can demonstrate that the device is safe and effective over the long term in primates and then humans, virtually every patient could be eligible for this treatment in the near future,” he explained.

Nicolelis and colleagues are already working with a team from from Brazil’s Edmond and Lily Safra International Institute of Neuroscience in Natal, to test the device in primate models of Parkinson’s, after which they hope to start clinical trials.

“Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson’s Disease.”
Romulo Fuentes, Per Petersson, William B. Siesser, Marc G. Caron, and Miguel A. L. Nicolelis.
Science 20 March 2009 323: 1578-1582.
DOI: 10.1126/science.1164901

Click here for Abstract.

Sources: Journal article, Duke Medicine News and Communications.

Written by: Catharine Paddock, PhD