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Spinal Cord Stimulator Sparks Hope For Parkinson's Disease Treatment



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New research of stimulation of the spinal cord
instead of the brain shows promise of countering
movement disorders associated with Parkinson's disease.

Video from Duke University shows what has been
accomplished. That video is on the PIENO maillist page at:

http://parkinsons-information-exchange-network-online.com/maillist.html

Perhaps annual additions to the "Hole in the Head
Gang" won't be necessary if this proves to be a viable non-invasive treatment.

John Cottingham



Novel Spinal Cord Stimulator Sparks Hope For Parkinson's Disease Treatment

ScienceDaily (Mar. 21, 2009) ­ A novel
stimulation method, the first potential therapy
to target the spinal cord instead of the brain,
may offer an effective and less invasive
approach for Parkinson's disease treatment,
according to pre-clinical data published in the
journal Science by researchers at Duke University Medical Center.

Researchers developed a prosthetic device that
applies electrical stimulation to the dorsal
column in the spinal cord, which is a main
sensory pathway carrying tactile information
from the body to the brain. The device was
attached to the surface of the spinal cord in
mice and rats with depleted levels of the
chemical dopamine ? mimicking the biologic
characteristics of someone with Parkinson's
disease along with the impaired motor skills
seen in advanced stages of the disease.

When the device was turned on, the
dopamine-depleted animals' slow, stiff movements
were replaced with the active behaviors of
healthy mice and rats. Improved movement was
typically observed within 3.35 seconds after stimulation.

"We see an almost immediate and dramatic change
in the animal's ability to function when the
device stimulates the spinal cord," says senior
study investigator Miguel Nicolelis, M.D.,
Ph.D., the Anne W. Deane Professor of
Neuroscience at Duke. "Moreover, it is easy to
use, significantly less invasive than other
alternatives to medication, such as deep brain
stimulation, and has the potential for
widespread use in conjunction with medications
typically used to treat Parkinson's disease."

Researchers tested mice and rats with acute and
chronic dopamine deficit using varying levels of
electrical stimulation and in combination with
different doses of dopamine replacement therapy,
also known as 3,4-dihydroxy-L-phenylalanine or
L-DOPA, to determine the most effective pairing.

When the device was used without additional
medication, Parkinsonian animals were 26 times
more active. When stimulation was coupled with
medication, only two L-DOPA doses were needed to
produce movement compared to five doses when the medication was used by itself.

"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," explains Romulo Fuentes,
a postdoctoral fellow at Duke University and
lead author of the study. "Patients are left
with few options for treatment, including
electrical stimulation of the brain, which is
appropriate for only a subset of patients."

While deep brain stimulation (DBS) and other
experimental treatments attack the disease at
its origin ? in the brain ? Nicolelis and team
took a different approach. The concept for the
device began when researchers made a surprising
connection with another neurological condition.

"It was a moment of sudden insight," explains
Nicolelis. "We were analyzing the brain activity
of mice with Parkinson's disease and suddenly it
reminded me of some research I'd done in the
epilepsy field a decade earlier. The ideas began to flow from there."

The rhythmic brain activity in the animals with
Parkinson's disease resembled the mild,
continuous, low-frequency seizures that are seen
in those with epilepsy. One effective therapy
for treating epilepsy involves stimulating the
peripheral nerves, which facilitate
communication between the spinal cord and the
body. Researchers took that concept and
developed a modified approach for a Parkinson's disease model.

Nicolelis says that the low frequency seizures,
or oscillations, seen in the animal model of
Parkinson's disease have been observed in humans
with the condition. Stimulating the dorsal
column of the spinal cord reduces these
oscillations, which researchers believe creates
the ability to produce motor function.

In a healthy body, neurons fire at varying rates
as information is transmitted between the brain
and the body to initiate normal movement. This
process breaks down in someone with Parkinson's disease.

"Our device works as an interface with the brain
to produce a neural state permissive for
locomotion, facilitating immediate and dramatic
recovery of movement," says Per Petersson,
co-author of the study. "Following stimulation,
the neurons desynchronize, similar to the firing
pattern that you would see when a healthy mouse is continuously moving."

Nicolelis says that if the device is proven safe
and effective through further research, he
imagines it mirroring similar spinal cord
stimulator technology currently used to treat
chronic pain. Small leads are implanted over the
spinal cord and then connected to a portable
generator, a small device capable of producing
mild electrical currents. During the trial
period, the generator is external, while for
permanent treatment it would be implanted below the skin.

"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," Nicolelis said.

The Duke team is collaborating with
neuroscientists at the Edmond and Lily Safra
International Institute of Neuroscience in
Natal, Brazil, to test the new procedure in
primate models of Parkinson's disease prior to
initiating clinical studies. Neuroscientists
from the Brain and Mind Institute at the Swiss
Institute of Technology (EPFL), in Lausanne,
Switzerland, will also participate in this
international research effort to translate these
new findings into clinical practice.

Study co-authors include William Siesser and Marc Caron.

Funding for this research was provided by grants
from the National Institutes of Neurological
Disorders and Stroke (NINDS), International
Neuroscience Network Foundation (INNF) and the Anne W. Deane Endowed Chair.

----------
Adapted from materials provided by Duke University Medical Center.
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Duke University Medical Center (2009, March 21).
Novel Spinal Cord Stimulator Sparks Hope For Parkinson's Disease Treatment

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