UW researchers show stem cell therapy may fight Lou Gehrig's disease
WTN News • Published 08/01/07
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Madison, Wis. - Using engineered stem cells, a team of scientists
from the University of Wisconsin-Madison has shown it is possible to
rescue the dying neurons characteristic of amyotrophic lateral
sclerosis (ALS), the fatal neuromuscular disorder also known as Lou
Gehrig's disease.
The new work, conducted in a rat model, was reported July 31 in the
online, open-access journal from the Public Library of Science, PLoS
ONE.
It demonstrates that stem cells engineered to secrete a key growth
factor can protect the motor neurons that waste away as a result of
ALS, the cause of which is unknown. An important caveat, according to
UW-Madison neuroscientist Clive Svendsen, is that while the motor
neurons within the spinal cord are protected by the growth factor,
their ability to maintain connections with the muscles they control
was not observed.
"At the early stages of disease, we saw almost 100 percent protection
of motor neurons," Svendsen said in a UW-Madison press release, "but
when we looked at the function of these animals, we saw no
improvement. The muscles aren't responding."
There are no effective treatments for ALS, which afflicts
approximately 40,000 people in the United States and is almost always
fatal within three to five years of diagnosis. ALS patients gradually
experience progressive muscle weakness and paralysis as the motor
neurons that control muscles are destroyed by the disease.
Engineered cells
In the new Wisconsin study, nascent brain cells known as neural
progenitor cells, which were derived from human fetal tissue, were
engineered to secrete a chemical known as glial cell line derived
neurotrophic factor (GDNF), an agent that has been shown to protect
neurons but is difficult to deliver to specific regions of the brain.
The engineered cells were then implanted in the spinal cords of rats
afflicted with a form of ALS.
GDNF had a very high affinity for motor neurons in the spinal cord.
When implanted, the GDNF-secreting cells "survive beautifully,
Svendsen said, "and in 80 percent of the animals, we saw nice
maturing transplants.
Perhaps more importantly, the implanted cells demonstrated an
affinity for the areas of the spinal cord where motor neurons were
dying. Svendsen said the cells migrate to the area of damage, where
they "just sit and release GDNF."
While the motor neurons exposed to GDNF were protected, the Wisconsin
team was unable to detect the connections between the neurons and the
muscles they govern.
The next step will be to determine the reasons that protected motor
neurons are unable to hook up with muscles, but Svendsen said the
work also supports movement toward clinical trials in humans.
"We think the cells are safe, and they do increase the survival of
the motor neurons," he said. "This may be very important for patients
that lose neurons every day."
Swendsen led the study at UW-Madison's Waisman Center with colleague
Masatoshi Suzuki. It was supported by grants from The ALS Association
and the University of Wisconsin Foundation.
In addition to Svendsen and Suzuki, authors of the study include
Jacalyn McHugh, Craig Tork, Brandon Shelly and Sandra M. Klein, all
of the Waisman Center; and Patrick Aebischer, of the Swiss Ecole
Polytechnique Fédérale de Lausanne.
http://wistechnolog
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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