Spinal Cord Stimulation Brings New Hope For Parkinson's Patients
20 Mar 2009 - 1:00 PDT
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.
Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
rbrown@xxxxxxxxx
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