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Assignment 2 Psychology 486 / 686
Chapter 9: Overview of the Motor System
Stem Cell Treatment for Motor Disorders
Recent research on motor disorders, including Parkinson’s disease and spinal
cord damage, has examined the use of stem cells as a possible treatment.
However, this research has been controversial. Learn how stem cells have been
used to treat Parkinson’s disease in readings 1,2. In readings 3,4 learn about the
use of stem cells for treatment of spinal cord injury. After reading the articles,
what is your opinion of the use of stem cells for treatment of motor disorders?
Does the research show enough promise to continue down this controversial
path? Do you think that stem cells will become more than an experimental
treatment in the near future? Write a two-page paper that responds to the above
questions. Make sure you include examples from the articles you read to support
your opinion.
Reading 1 : Website: http://www.newsmedical.net/news/2007/07/11/27436.aspx
Neural Stem Cells for Parkinson’s Disease
11. July 2007 13:39
A University of South Florida neuroscientist reports that the cutting-edge
research study of human stem cells in primates with Parkinson's disease
is compelling on several fronts , particularly how the transplanted cells
did their job of easing disease symptoms.
Paul R. Sanberg, DSc, PhD, Distinguished Professor of Neurosurgery and
Director of the Center for Aging and Brain Repair at USF Health, wrote the
commentary "Neural Stem Cells for Parkinson's Disease: To Protect and
Repair", published July 9 in the 'Early Edition' online version of journal
Proceedings of the National Academy of Sciences of the United States of
America (PNAS). The expert commentary is a companion piece to the study
conducted by Gene Redmond and colleagues at Yale and Harvard Universities
and the Burnham Institute.
That NIH-funded study showed that only a small number of stem cells turned
into dopamine-producing cells , not enough to improve the primates, function by
replacing missing neurons. Instead, some stem cells turned into astrocytes, a
supportive brain cell that produces neuron-nourishing chemicals. The
researchers also identified in the brains of the primate recipients a significant
amount of dopamine-producing neurons that were not derived from stem cells.
The results suggest that stem cells may actually trigger the brain's own selfrepair mechanisms by pumping out molecules that boost nerve survival and
blood vessel development and decrease neural degeneration.
"We at the Center for Aging and Brain Repair at USF Health have been arguing,
for some time now, that stem cells are important for brain repair because they
provide growth factors and because they send signals to the brain to help it
repair itself," Dr. Sanberg said. "This study in primates showed the same effects
-- that the stem cells are there to act as facilators of repair versus the original
hypothesis that stem cells are transplanted to merely replace an injured cell."
Dr. Sanberg said the study has relevance to all audiences. "This was one of the
first studies to look at stem cells in primates with Parkinson's disease. It's the
first step in translating that research," he said. "We hear about new sources of
stem cells monthly, but how we take those cells and treat disease is going to be
a significant amount of translational work. This is one of the first studies that
starts that process - looking at primates before going into people with
Parkinson's disease."
While the transplanted cells appeared not to form tumors following transplant,
Dr. Sanberg said the translational research in primates raises questions that
need to be addressed before moving to human trials, including determining the
most effective cell dosing and brain sites to target.
"Pending further preclinical studies," he concludes in the commentary, "the
results so far from the current study are supportive for developing a safe and
effective stem cell treatment for Parkinson's disease."
Dr. Sanberg's commentary and the study it highlights will also be published in
the magazine edition of PNAS. The global journal has been a resource for
multidisciplinary research since 1914. Its online edition, where Dr. Sanberg's
commentary appears this week, receives nearly 6 million e-visitor 'hits' per
month. Content includes research reports, commentaries, reviews,
perspectives, colloquium papers, and actions of the Academy. Coverage in
PNAS spans the biological, physical, and social sciences.
http://www.hsc.usf.edu
Reading 2: Website: http:/washingtonpost.com/wpdyn/content/article/2006/10/22/AR2006102200928_pf.html
Stem Cell Work Shows Promise and Risks
Parkinson's Treatment Tried in Rats Reduced Symptoms but Caused Tumors
By Rick Weiss
Washington Post Staff Writer
Monday, October 23, 2006
Nerve cells grown from human embryonic stem cells and injected into the brains
of rats with a syndrome mimicking Parkinson's disease significantly reduced the
animals' symptoms, but the treatment also caused tumors in the rodents' brains,
scientists reported yesterday.
Researchers said the work showed both the potential benefits and risks of
human embryonic stem cells, which have been highly touted for their capacity to
replace diseased tissue but are controversial because they are derived through
the destruction of human embryos.
"The behavioral data validate the utility of the approach. But it also raises a
cautionary flag and says we are not ready for prime time yet," said lead
researcher Steven A. Goldman, a professor of neurology and neurosurgery at the
University of Rochester Medical Center.
Goldman said he suspected that with modest changes in technique, researchers
will be able to keep the benefits of the treatment while eliminating or reducing the
chances of getting the cancerlike growths. But he conceded that much more
basic research would have to be done before scientists -- or regulators -- were
likely to be convinced of the approach's safety.
In the experiments, Goldman and colleagues from the Weill Medical College of
Cornell University in New York treated laboratory-cultured human embryonic
stem cells in a new way that coaxed many to become a kind of neuron that
produces dopamine, a neurotransmitter. Those cells are gradually lost in
Parkinson's disease, depriving the body of that essential chemical messenger.
The disease causes motor problems such as trembling and muscle rigidity and a
gradual decline in mental functioning.
The team injected the cells into the brains of rats, which had been given a
chemical that causes damage similar to that seen in Parkinson's. The new cells
integrated into the animals' brains and produced copious amounts of dopamine.
As a result, the animals' motor coordination improved almost to the point of being
normal, according to the report in yesterday's online edition of the journal Nature
Medicine.
But when the animals were autopsied after three months and their brains were
examined microscopically, the team found multiple tumors, indicating that some
of the injected cells did not settle into the job of being neurons but rather had
begun to grow uncontrollably.
The results were similar to those of other experiments published Oct. 12 in the
online journal Stem Cells by a team led by Ole Isacson, a Harvard Medical
School professor of neuroscience and neurology. In that case, the stem cells
were cultivated differently, produced less dopamine and had fewer beneficial
effects. But some grew out of control. "I think it is a terrific demonstration that we
are midway between earliest discovery and clinical application," Isacson said
Friday.
Goldman and Isacson said they are developing technologies for culling from a
developing stem cell population those cells that are not fully committing
themselves to becoming neurons -- or selecting such fully committed cells from a
larger, mixed population.
"We still have so little experience with these cells, but if we keep doing the work
and we do it carefully, then I believe that in the long run it will help patients,"
Isacson said.
Thomas Okarma, president of Geron, a California company that hopes to gain
Food and Drug Administration permission to treat spinal-cord-injury patients with
modified embryonic stem cells next year, said his company's cells have shown
no sign of causing tumor growth in any of its animal studies. But he said the FDA
has asked for additional extensive data on exactly that question before it will give
its final okay. "What they worry about, and rightly so, is there are rogue
undifferentiated cells lurking in the cell population that we haven't detected,"
Okarma said.
Geron cultivates its embryonic stem cells differently than others, he said, adding
that no tumors have been seen in animals up to nine months after injections into
the rodents' injured spinal cords. Moreover, he said, the cells survive and help
the animals recover, in part by secreting special factors that spur new nerve
growth around the injury.
Reading 3:
Website: http://www.medicalnewstoday.com/articles/24159.php
Stem cell treatment improves mobility after spinal cord injury
11 May 2005
A treatment derived from human embryonic stem cells improves mobility in rats
with spinal cord injuries, providing the first physical evidence that the therapeutic
use of these cells can help restore motor skills lost from acute spinal cord tissue
damage.
Hans Keirstead and his colleagues in the Reeve-Irvine Research Center at UC
Irvine have found that a human embryonic stem cell-derived treatment they
developed was successful in restoring the insulation tissue for neurons in rats
treated seven days after the initial injury, which led to a recovery of motor skills.
But the same treatment did not work on rats that had been injured for 10 months.
The findings point to the potential of using stem cell-derived therapies for
treatment of spinal cord damage in humans during the very early stages of the
injury. The study appears in the May 11 issue of The Journal of Neuroscience.
"We're very excited with these results. They underscore the great potential that
stem cells have for treating human disease and injury," Keirstead said. "This
study suggests one approach to treating people who've just suffered spinal cord
injury, although there is still much work to do before we can engage in human
clinical tests."
Acute spinal cord damage occurs during the first few weeks of the injury. In turn,
the chronic period begins after a few months. It is anticipated that the stem cell
treatment in humans will occur during spinal stabilization at the acute phase,
when rods and ties are placed in the spinal column to restabilize it after injury.
Currently, drug treatments are given during the acute phase to help stabilize the
injury site, but they provide only a very mild benefit, and they do not foster
regeneration of insulation tissue.
For the study, the UCI team used a novel technique they created to entice
human embryonic stem cells to differentiate into early-stage oligodendrocyte
cells. Oligodendrocytes are the building blocks of myelin, the biological insulation
for nerve fibers that is critical for maintenance of electrical conduction in the
central nervous system. When myelin is stripped away through disease or injury,
sensory and motor deficiencies result and, in some cases, paralysis can occur.
The researchers injected these cells into rats that had experienced a partial injury
to the spinal cord that impairs walking ability -- one group seven days after injury
and another 10 months after injury. In both groups, the early-stage cells formed
into full-grown oligodendrocyte cells and migrated to appropriate neuronal sites
within the spinal cord.
In the rats treated seven days after the injury, myelin tissue formed as the
oligodendrocyte cells wrapped around damaged neurons in the spinal cord.
Within two months, these rats began to show significant improvements in walking
ability in comparison to injured rats who received no treatment.
In the rats with 10-month-old injuries, though, motor skills did not return. Although
the oligodendrocyte cells survived in the chronic injury sites, they could not form
myelin because the space surrounding neuron cells had been filled with scar
tissue. In the presence of a scar, myelin could not grow.
These studies indicate the importance of myelin loss in spinal cord injury, and
illustrate one approach to treating myelin loss. Keirstead and his colleagues are
currently working on other approaches using human embryonic stem cells to
treat chronic injuries and other disorders of the central nervous system.
In previous studies, Keirstead and colleagues identified how the body's immune
system attacks and destroys myelin during spinal cord injury or disease states.
They also have shown that when treated with antibodies to block immune system
response, myelin is capable of regenerating, which ultimately restores sensory
and motor activity.
Oswald Steward, Gabriel I. Nistor, Giovanna Bernal, Minodora Totiu, Frank
Cloutier and Kelly Sharp also participated in the study, which was supported by
the Geron Corp., a UC Discovery grant, Research for Cure, the Roman Reed
Spinal Cord Injury Research Fund of California and individual donations to the
Reeve-Irvine Research Center. Geron provides the human embryonic stem cells
for Keirstead's research.
The Reeve-Irvine Research Center was established to study how injuries and
diseases traumatize the spinal cord and result in paralysis or other loss of
neurologic function, with the goal of finding cures. It also facilitates the
coordination and cooperation of scientists around the world seeking cures for
paraplegia, quadriplegia and other diseases impacting neurological function.
Named in honor of Christopher Reeve, the center is part of the UCI School of
Medicine.
About the University of California, Irvine: Celebrating 40 years of innovation, the
University of California, Irvine is a top-ranked public university dedicated to
research, scholarship and community service. Founded in 1965, UCI is among
the fastest-growing University of California campuses, with more than 24,000
undergraduate and graduate students and about 1,400 faculty members. The
second-largest employer in dynamic Orange County, UCI contributes an annual
economic impact of $3 billion. For more UCI news, visit
http://www.today.uci.edu/experts.
UCI maintains an online directory of faculty available as experts to the media. To
access, visit http://www.today.uci.edu/experts.
Contact: Tom Vasich
[email protected]
949-824-6455
University of California - Irvine
http://www.uci.edu
Reading 4: Website:
http://www.sciencedaily.com/releases/2007/11/071112172133.htm
First Steps Towards Spinal Cord Reconstruction Following Injury
Using Stem Cells
ScienceDaily (Nov. 13, 2007) — A new study has identified what may be a
pivotal first step towards the regeneration of nerve cells following spinal cord
injury, using the body's own stem cells.
This seminal study, published in this week's Proceedings of the National
Academy of Science, identifies key elements in the body's reaction to spinal
injury, critical information that could lead to novel therapies for repairing
previously irreversible nerve damage in the injured spinal cord.
Very little is known about why, unlike a wound to the skin for example, the adult
nervous system is unable to repair itself following spinal injury. This is in contrast
to the developing brain and non-mammals which can repair and regenerate after
severe injuries. One clue from these systems has been the role of stem cells and
their potential to develop into different cell types.
"Because of their regenerative role, it is crucial to understand the movements of
stem cells following brain or spinal cord injury," says Dr. Philip Horner, co-lead
investigator and neuroscientist at the University of Washington. "We know that
stem cells are present within the spinal cord, but it was not known why they could
not function to repair the damage. Surprisingly, we discovered that they actually
migrate away from the lesion and the question became why - what signal is
telling the stem cells to move."
The researchers then tested numerous proteins and identified netrin-1 as the key
molecule responsible for this migratory pattern of stem cells following injury. In
the developing nervous system, netrin-1 acts as a repulsive or attractive signal,
guiding nerve cells to their proper targets. In the adult spinal cord, the
researchers found that netrin-1 specifically repels stem cells away from the injury
site, thereby preventing stem cells from replenishing nerve cells.
"When we block netrin-1 function, the adult stem cells remain at the injury site,"
says Dr. Tim Kennedy, co-lead investigator and neuroscientist at the Montreal
Neurological Institute of McGill University. "This is a critical first step towards
understanding the molecular events needed to repair the injured spinal cord and
provides us with new targets for potential therapies."
This study was funded by the Craig H Nielsen Foundation and the National
Institutes of Health.