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Paralyzed Rats Walk; Humans Next? 

Wired News | May 12, 2005
By Kristen Philipkoski

Researchers studying embryonic stem cells have published long-awaited data in a peer-reviewed journal, revealing how they enabled rats with crushed spinal cords to walk again. Spinal cord injury patients are hopeful, but they're not all celebrating just yet.

The publication is certainly a step in a promising direction for the treatment of patients with damaged spinal cords. But the study found that the technique worked only on recently injured rats, not those with chronic injuries. The researchers say they hope to begin human clinical trials sometime soon, but the tests will likely study only newly injured patients.

It's a disappointment to many patients who have been waiting for years for a treatment that might get them out of their wheelchairs. But the disappointment is not entirely unexpected.

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"I don't get too excited about much research nowadays," said Steven Edwards, 25, who injured his spinal cord in a car accident in 1996. "I think the research is good, but I think it's not the best there is out there. It's 3 years old, and there are other combination therapies that are showing as good or better results. I would rather see those in the news."

Hans Keirstead, an assistant professor of anatomy and neurobiology at the Reeve-Irvine Research Center , has been showing video of his rats since 2002 . One clip shows a rat dragging its feet, unable to lift its tail. In the next clip, the rat can lift its tail high, bear its own weight and move about. Keirstead reported the rats also regained bladder and bowel functions.

Keirstead and his colleagues now share their data in the May 11 issue of The Journal of Neuroscience .

"My reaction to the study finally being published is delight," said John Smith, whose son Noah suffered a spinal cord injury in December 2002 when he was 22. The time elapsed since Noah Smith's accident qualifies his injury as " chronic ."

"My reaction to the study's findings that (the treatment) is not applicable to chronic (spinal cord injury) is mixed," said John Smith. "The peer-review process is slow and this research is already dated somewhat."

Smith and his son visited Keirstead and other scientists at the University of California at Irvine in March, and were encouraged to learn that researchers have already begun additional animal studies, and that they anticipate beginning human clinical trials as soon as 2006.

Christopher Chappell, who also visited UC-Irvine in March, is thrilled about the publication despite the fact that the technique as it stands will not address chronic patients. After a mountain biking accident left him paralyzed from the chest down five years ago, Chappell became active in the CareCure newsgroup, whose members closely follow, share information about and argue over the work of many spinal cord injury researchers.

"I went back to the (CareCure) community (after the visit) and told them I think this is the guy we need to back because it's rare we get a scientist willing to be as aggressive and has the same urgency as the community does," Chappell said. "He is looked at as a maverick by scientists, but the injured community looks at him as kind of a hero, because he's willing to take a chance."

Other therapies deserve as much, if not more, attention as embryonic stem-cell research, said Edwards, who is also a member of CareCure. For example, Mary Bunge at the Miami Project to Cure Paralysis , is making progress with Schwann cells .Martin Schwab is studying ways to inhibit proteins that prevent the spinal cord from repairing itself. Others, including Keirstead, believe olfactory ensheathing cells, which can be taken from the mucosal lining of the nose, show promise as a potential treatment for paralysis.

"It's worthwhile to note that in the midst of all this excitement over stem cells, a lot of tremendously exciting and equally promising non-stem-cell research" is addressing spinal cord injuries, said Susan Howley, executive vice president of the Christopher Reeve Paralysis Foundation .

But embryonic stem cells get attention because they're taken from microscopic embryos that are destroyed in the process. Many scientists believe the cells will lead to treatments for many diseases, and they're determined to pursue the research despite President Bush's limits on federal funding of stem-cell studies.

In Keirstead's latest study, the scientists injected injured rats with cells derived from human embryonic stem cells, which usually come from embryos discarded at in vitro fertilization clinics. Keirstead and his colleagues coaxed the embryonic cells into becoming early-stage cells critical for normal electrical signal processing in the spine.

The researchers injected one group of rats seven days after injury, and another group 10 months after injury. In all of the mice, the cells became mature cells and migrated to areas of the spinal cord where they were most needed. In the recently injured rats, the cells, called oligodendrocytes, formed myelin, a protective insulator of neurons. The myelin wrapped around damaged neurons in the spinal cord, and within two months the rats were walking much better than injured rats that received no treatment.

But the rats with 10-month-old injuries failed to regain motor skills. Although the oligodendrocyte cells survived in the chronic injury sites, the researchers said in a press release that scar tissue surrounding the neurons prevented the cells from forming myelin.

The slow progress of science frustrates many patients with all types of disorders, leading some to seek out risky treatments. But aggressive scientists like Keirstead are moving fast enough to satisfy many, and hopefully prevent them from jeopardizing their safety by pursuing unproven therapies.

"What we have to do in this community is make a balance between desperation and patience," Chappell said. "Many patients will just do anything they can to try to restore function, and sometimes that means they'll engage in things that are unsafe. You rarely get someone at Hans' caliber to actually publish something peer reviewed that the community can grasp onto."

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