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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:

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 self-repair 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.



Reading 2: Website: http:/wp-dyn/content/article/2006/10/22/AR2006102200928_pf.html

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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:

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 .

UCI maintains an online directory of faculty available as experts to the media. To access, visit .

Contact: Tom Vasich

tmvasich@uci.edu

949-824-6455

University of California - Irvine



Reading 4: Website:

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.

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