- Research published in the current issue of The Journal of
Neuroscience shows a human neural stem cell transplant essentially
enables an animal model for Parkinson's to continue functioning
normally rather than displaying the progressive loss of movement
control that characterizes the disease.
"We are very cautious but to us, it's an indication that stem cells
have promise for Parkinson's disease," says Dr. Cesario V.
Borlongan, neuroscientist at the Medical College of Georgia and
corresponding author of the study.

Transplants were done shortly after a neurotoxin was used to destroy
neurons that make dopamine, a neurotransmitter key to movement
control, Dr. Borlongan notes. This would be equivalent to a patient
getting treatment very early in the disease process, which rarely
happens since there is no screening test to catch it early.

"Right now we are saying if you are able to identify Parkinson's in
the early stage, we think this therapy will work. An important
question that remains is, `Can we rescue neurons that are dying from
Parkinson's"' This would more accurately mimic what patients need."
The researchers already have begun studies that delay the
transplants until weeks after injury.

For this study, researchers compared animals that received placebo
treatment with those that received only protective neurotrophic
factors secreted by stem cells and those that had a transplant.

Animals that received transplants essentially regained control of
their movement, placebo-treated animals did not recover and those
that received neurotrophic factors, called stem cell factors,
recovered partially.

When researchers examined the brains one month after transplant – a
long time in the two-year life of a rat - researchers found
endogenous dopaminergic cells and transplanted neural stem cells had
both survived. Also, transplanted neural cells had formed synapses
to communicate with each other and ultimately the striatum, the
portion of the brain dopaminergic cells act on to control movement.

"When we looked at the transplanted stem cells, they had survived,
had differentiated into neurons and showed some connection with the
host tissue," says Dr. Borlongan.

They did additional studies in test tubes, taking commercially
available rat and human dopaminergic cells, exposing them to
neurotoxins and then to stem cell factors. Stem cell factor
protected cells in a dose-dependent fashion. "The more stem cell
factor, the better the protection," Dr. Borlongan says. When the
cells were co-cultured with stem cells, protection was further
increased. When they used an antibody to block the stem cell factor,
neuro-protection was significantly reduced. "This again shows a
combination of factors at work," says Dr. Borlongan. "It's a
synergistic effect."

He's now following rats with transplants for six months to see if
the early protection/recovery holds up; he's already past the three-
month mark and to date, recovery is stable. While the rats needed
immunosuppression because they received human cells, Dr. Borlongan
says humans would not.

About a half-million Americans have Parkinson's disease. Typically
the disease does a lot of damage to dopaminergic cells before it
becomes symptomatic. Although Parkinson's is associated with
abnormal movement, such as tremors, loss of these cells actually
makes it difficult for people to move and, once they move, they
can't control the movement, Dr. Borlongan says. The standard
treatment is L-dopa, a synthetic dopamine that tends to minimize
symptoms for three to five years. As the disease progresses and the
drug becomes less effective, doses are increased and can produce
more dyskinesia, loss of controlled movement. Centers such as MCG
are exploring new ways to slow disease progression, diagnose it
earlier and more accurately monitor its progression.


12/04/06(Medical College of Georgia