Tuesday, January 27, 2004

When Will Stem Cells Heal Spinal Cord Damage?

They hold huge promise, but stem cell-based spinal cord treatments won't be clinically available in the near future
Answered by Aileen J. Anderson ~ 1/22/2004

My three-year-old son was born with a very large spinal lipoma. He was considered quadriplegic. Through conventional physical and occupational therapies and surgery to remove some of the lipoma he has gained enough function to walk with a walker and use his arms. However, he is experiencing some regression as his nerves are dying.

I have saved the cord blood from his younger brother and sister. New research where mice are being paralyzed and then injected with stem cells looks very promising to us. The mice nerves that are sick or weak are being protected and strengthened. Our son needs his nerves protected from degeneration.

Conventional surgery is no longer an option because the nerve roots travel in and out of the lipoma and cannot be separated from the lipoma. Our only hope is to protect and strengthen what function he currently has.

My question is: How long before this type of stem cell therapy will be used on humans, more specifically children? And how do we get to be first in line? If it is 10 or 20 years away, there may be no way to save the function our son has worked so hard to gain. I haven't read anything about risks or side effects. There have to be some, what are they? Also, are there other countries that are more aggressive in their use of stem cells on humans for treating paralysis resulting from spinal cord injury?

Barbara Bourgeois
Centreville, Virginia, USA

There isn't an easy answer here, and I'm not clear as to why function is being lost at this point—in particular, whether the lipoma is recurring. If this is the case, resolution of the lipoma is the main issue. In some instances, it is impossible to completely remove the tumor, severely limiting the potential benefits of secondary therapeutics (such as stem cells). However, on the topic of stem cells in particular, there are several issues to discuss.

First, there are many sources of stem cells, and this affects their potential clinical use. Cord blood-derived stem cells are probably the farthest away from potential clinical use for spinal cord injury at this point, because there has been less basic research done with them so far. Human embryonic and adult stem cell lines may be somewhat closer, but research on these in the laboratory has been somewhat mixed—some very promising results with regaining motor function, and some big potential concerns, such as causing tumor formation.

As a result, we are most likely still years away from testing these treatments in patients, even to establish safety. Some other kinds of cell treatments, such as ensheathing glial cells, are being tried in the clinic in China, Russia and Portugal based on previous laboratory research in the US. However, none of these overseas trials has been designed in accordance with US standards to rigorously test safety and efficacy, and it is very difficult to evaluate the patchy data coming out so far.

To sum up, as a researcher, I think stem cells hold a huge amount of promise, but we aren't yet at a point where this work will be translated to the clinic in the immediate future.
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Nanofiber Gel Could Heal Spinal Damage

Nanofiber Gel Could Heal Spinal Damage
By Dwayne Hunter, Betterhumans Staff

A gel of tiny fibers could help reverse paralysis from spinal cord injury.

The gel, created by scientists from Northwestern University in Evanston, Illinois, contains a three-dimensional network of nanoscale fibers that form a scaffold to promote neuron growth.

'We have created new materials that because of their chemical structure interact with cells of the central nervous system in ways that may help prevent the formation of the scar that is often linked to paralysis after spinal cord injury,' says research leader Samuel Stupp, director of Northwestern's Institute for Bioengineering and Nanoscience in Advanced Medicine.

Stopping scars.
Following spinal cord injury the body can produce cells called astrocytes.
Astrocytes lead to scarring and hinder injury repair, which can cause paralysis.
Stupp and colleagues have shown that their scaffold directs cell differentiation so that neural progenitor cells become neurons and not astrocytes.

The scaffold contains nanofibers made of molecules called peptide amphiphiles.
Normally, the molecules repel each other and remain liquid, but positively charged molecules such as the calcium in living tissue causes them to clump together.
They clump in such a way that they self-assemble into porous tubes about five nanometers wide and several hundred nanometers long.

Directing cells
To encourage neuron growth, Stupp and colleagues added a biological 'signal' to the mix.

When their peptide amphiphiles self-assemble into nanofibers, they present on their surface a sequence of five amino acids known to promote neuron growth.
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Neurons from nanostructures

Neurons from nanostructures

Scientists at Northwestern University in the US have designed synthetic molecules that promote neuron growth, a development that could lead to the reversal of paralysis due to spinal cord injury.

'We have created new materials that, because of their chemical structure, interact with cells of the central nervous system in ways that may help prevent the formation of the scar that is often linked to paralysis after spinal cord injury,' said Samuel I Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry and Medicine.

Similar to earlier experiments that promoted bone growth, the scientists have grown nerve cells using an artificial three-dimensional network of nanofibres, an important technique in regenerative medicine.

'We have shown that our scaffold selectively and rapidly directs cell differentiation, driving neural progenitor cells to become neurons and not astrocytes,' said Stupp, who led the research team in Evanston. 'Astrocytes are a major problem in spinal cord injury because they lead to scarring and act as a barrier to neuron repair.'

The scaffold is made up of nanofibres formed by peptide amphiphile molecules. According to a statement, the scientists' key breakthrough was designing the peptide amphiphiles so that when they self-assembled into the scaffold a specific sequence of five amino acids known to promote neuron growth were presented in enormous density on the outer surfaces.

'This was all done by design,' said Stupp. 'By including a specific biological signal on the nanostructure we were able to customise the new materials for neurons.'
In collaboration with the lab of John A. Kessler, Benjamin and Virginia T. Boshes Profe"
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Study: Muscles respond to getting on your feet after spinal cord injury

Study: Muscles respond to getting on your feet after spinal cord injury

When someone's spinal cord is completely severed, brain signals can no longer reach the legs to tell the legs to walk.

A study in this month's journal Spinal Cord shows that those who have suffered a spinal cord injury can generate muscle activity independent of brain signals. Dan Ferris, now an assistant professor of kinesiology at U-M, led the research as part of his post-doctorate work with Susan Harkema at University of California Los Angeles David Geffen School of Medicine.

While many studies have shown that locomotor training, such as working with patients on treadmills, is a viable therapy for helping those who have suffered a spinal cord injury learn to walk again, Ferris and his UCLA colleagues added further evidence that adding weight to the limbs during therapy can provide an important sensory cue to help regain walking.

They also found that moving one leg in therapy can help activate muscles in the opposite leg.

"Nobody has been able to show that in humans before," said Ferris, also an assistant professor of biomedical engineering. "It appears there are left-to-right connections in the signal in the spinal cord, not just connections from the brain to the legs."

The research was partially supported by five grants from the National Institutes of Health.

The team worked with four patients with clinically complete spinal cord injury, doing about 30 sessions with each over about 1.5 years. They hooked each subject into a harness suspended over a treadmill. Trainers helped move the subjects' legs as they stepped on the treadmill.

When the subjects were positioned so that just one leg was on the moving treadmill belt and the other was off the side, not touching the treadmill surface, the team was able to get muscle response in one leg by simulating walking with the other.

"If you step one leg, you can get muscle activation in the other, even when it isn't moving," Ferris said. "This shows that it isn't just muscle stretch that causes activitation."

Ferris and the team---Harkema, Keith Gordan and Janell Beres-Jones---see great potential in this information for developing rehabilitation strategies.

Therapists helping patients recover from spinal cord injury should provide sensory information that simulates walking as closely as possible. Weight loading and movement in one leg can influence what happens in the other leg.

The Christopher Reeve Paralysis Foundation is funding another project, led by Ferris, to build powered braces to help those with spinal cord injury regain the ability to walk. Ferris speculates that perhaps such braces could help move the legs to recreate a more normal stepping pattern during rehabilitation. Ferris is testing a working model of the braces to assist patients in walking.

Harkema is heading up a second project funded by the foundation to study the therapeutic effects of stand training after spinal cord injury.
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Wednesday, January 21, 2004

Paralyzed actor lauds 'critical' stem-cell research in Israel

Paralyzed actor lauds 'critical' stem-cell research in Israel
By STEPHANIE MURPHY, Daily News Business and Real Estate Writer
Wednesday, Jan. 21, 2004

Before science catches up with a cure for paralyzed equestrians, research breakthroughs are more likely in diabetes and Parkinson's Disease, actor Christopher Reeve said Sunday at The Four Seasons Resort.

Before Reeve or anyone else reaps such benefits, he said, opponents of embryonic stem-cell research will have to reconcile their concerns with what he witnessed last year in the treatment of spinal-cord injuries in Israel: "I saw very advanced work, work that is absolutely critical, going on in Israel."

Sweden, the United Kingdom and Singapore are following suit, Reeve said, "But Israel has a history of taking on complex issues. Keep in mind that the first and foremost purpose of applied science is to relieve human suffering. Perhaps we've lost sight of that here at home."

He addressed the gap in politics in the United States and Israel during a weekend symposium presented by the American Friends of Hebrew University. The star of Superman films, paralyzed from the neck down since a 1995 horseback-riding accident, Reeve was Saturday's keynote speaker. He held a press conference Sunday and participated in a panel, "Frontiers in Brain Research."

Reeve said the Bush administration and leaders in Israel "come to a very different conclusion" on ethics and morality. He referred to President Bush's order two years ago to limit federal money for embryonic stem-cell research to self-sustaining colonies of cells already extracted from human embryos. Bush said no new embryos could be taken for federally financed research.

Most cells depend on like-cells for regeneration. Medical researchers are especially focused on embryonic stem cells because they can evolve into cells of other types.

"That means embryonic stem cells can be put elsewhere in the body and given a new job," Reeve said.

"As much as I am an advocate for scientific freedom of inquiry, derived from any source, it's not about whether it will help me . . . But it may be the answer for people with Parkinson's and most likely diabetes. It may help me, or it may not."

Reeve said Hebrew University's progress has been dramatic in neural computation, or study of the brain. A scientist there who is working on spinal-cord regeneration could be ready for clinical trials within two years, he said.

There are studies indicating that the embryonic stem-cell research could eventually yield treatments for Alzheimer's, heart disease, cancer and injuries such as Reeve's. Several private groups, including the Christopher Reeve Paralysis Foundation, support the research elsewhere.

In The New York Times in March, lobbyist Michael Manganiello of the Coalition for the Advancement of Medical Research, said, "This research holds tremendous promise for medical breakthroughs for things like spinal cord injury and diabetes."

Many opponents say stem-cell research is immoral because human embryos are destroyed after cell extraction. Reeve said more than one-third of the fertilized embryos are "excess. If they are not frozen to make a sibling, they are discarded as medical waste. Why would it be immoral to save some of them from the garbage to use the cells for research?"

He said those who would criminalize the harvesting of cells also would block the importation of the technology: "So I could go to Israel and be treated, come back to New York and be arrested. It's absurd."

In 1996, philanthropist Lois Pope made a $10 million grant to the Miami Project to Cure Paralysis — a gift that was matched by the state of Florida. Pope had met Reeve at a local charity event before his accident.

Reeve's foundation, based in Springfield, N.J., has spawned a fund-raising consortium which gives research grants twice a year and has awarded $47 million to date, he said.

The foundation also has a resource center for the newly injured — "for people who experience what I experienced right after I was injured — total bewildering fear and a sense that life will never be normal again." The group has a new guide "for anyone, whether injured two days or 20 years." At his Web site are links to specialists: paralysis.org.

The group also has a quality-of-life grants program for assisted-living needs, transportation, recreation, job opportunities and accessibility. There are branches in New Jersey, Westchester County, N.Y., and Washington, D.C.

Reeve's paralysis resource center receives federal money each year from the Centers for Disease Control. Despite other budget cuts, support is in place, he said, "and we hope it will be continuing."

His visit to Israel was educational, not for treatment, because work there is focused on those with acute paralysis, within 14 days of injury, "and I missed that by a long shot."

Life is not "normal," he said, but it's "more than tolerable." Reeve and his family cope with their circumstances in a house filled with "a lot of laughter and joy."

He guards his health, so as not to "go backward. But as soon as I'm invited to a clinical trial that's safe, I'd go."
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Protein linked to nerve regeneration

Protein linked to nerve regeneration - (United Press International)
NEW YORK, Jan. 20 (UPI)

A study by the Weizmann Institute in New York has uncovered part of the process that could lead to the regeneration of peripheral nerves.

Peripheral nerves are nerves aside from the brain and spinal cord. They are capable of regenerating, but do so poorly and scientists hope that if the process was better understood, nerve regeneration could occur where it has been irreversible.

Nerve cells have a cell body containing the nucleus and a long 'arm,' called an axon, that can extend up to 1 yard. The axons are the main conduit for nerve communication conveying electric signals to muscles or other cells, but their length make them vulnerable to damage.

A study, published in Neuron, showed that a special protein -- called importin beta -- is produced at the site of nerve damage in the axon. It normally resides near the nucleus of nerve cells and facilitates the entry of molecules into the nucleus along with its 'sister' molecule, importin alpha.

Dr. Michael Fainzilber found importin beta was produced in the axons upon injury, binds it to importin alpha and to proteins containing the 'healing message.' "
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Tuesday, January 13, 2004

N.J. second state to allow stem cell research

WEST ORANGE, New Jersey (AP) --New Jersey became the second state to allow stem cell research as Gov. James E. McGreevey signed a law he said will "move the frontiers of science forward."

Stem cell research, which has been strongly opposed by anti-abortion groups and the Roman Catholic church because it involves the use of fetal and embryonic tissue, is also permitted in California and bills are pending in Illinois and New York.

McGreevey was joined Sunday by Christopher Reeve, the actor who was paralyzed by a 1995 fall from a horse and has become an advocate for increased funding for medical research.

"Today we celebrate the possible in our state," McGreevey said. "It is our obligation as a people and as a state to move the frontiers of science forward."

Stem cells are produced in the first days of pregnancy and help create the human body. Scientists hope to someday direct stem cells to grow into replacement organs and tissues to treat a wide range of diseases.

President Bush, citing ethical considerations, has limited federal funding for embryonic stem cell research to existing lines of cells.

Opponents of the bill said they were disappointed but not surprised that McGreevey signed it.

"We were hopeful that perhaps he would take the expert opinions and concerns into consideration before formulating his final decision, which unfortunately he did not," said Marie Tasy of New Jersey Right to Life.

Reeve said although many people have asked what stem cells could do to cure his spinal cord injury, "it is not about what stem cells will do for one individual."

"What it's about, this legislation, is about whether or not we have the courage to protect the freedom of ethical and responsible scientific inquiry," Reeve said.
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Eastern Paralyzed Veterans changes name

A national nonprofit veterans service and disability rights organization recently announced it was changing its name and broadening its mission.

The Eastern Paralyzed Veterans Association now known as the United Spinal Association will offer membership and service to any veteran, child or adult with a disability or disease of the spinal cord.

Medical advances, fewer numbers of veterans with spinal cord injuries and increases in spinal cord ailments in nonveterans from multiple sclerosis to amyotrophic lateral sclerosis and spina bifida were among the reasons the organization broadened its mission, said New City resident Gerard M. 'Jerry' Kelly, United Spinal's executive director.
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