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December 6, 2004

Study On Dogs Yields Hope In Human Paralysis Treatment

Topics: Medicine

SCRIPPS HOWARD NEWS SERVICE via seattlepi.com.

Researchers have successfully tested injections of a liquid polymer to heal spinal injuries in dogs in an experiment that also offers hope for preventing human paralysis.

The liquid, called polyethylene glycol (PEG), if administered within 72 hours of serious spinal injury, was able to prevent three out of four dogs in a test group from suffering permanent spinal damage. Even when the spine was damaged to the point of paralysis, the PEG solution prevented nerve cells from rupturing irreversibly, allowing them to heal themselves.

"Nearly 75 percent of the dogs we treated with PEG were able to resume a normal life," said Richard Borgens, director of the center for Paralysis Research at Purdue University's School of Veterinary Medicine in West Lafayette, Ind., which developed the treatment. "Some healed so well that they could go on as though nothing had happened."

While the polymer has been safely ingested by and injected in humans as a component of other medicines, and Borgens thinks it shows great promise as a human therapy, he cautions: "This is very promising research, but it won't be available in your hospital for some time."

The research is described in the December issue of the Journal of Neurotrauma.

When nerve cells suffer trauma, their membranes weaken and rupture. Even when the cells survive, they lose their ability to produce and carry nerve impulses along the membranes from one cell to the next.

"Worse yet, chemicals seeping out of the dying spinal cord cells send a 'suicide signal' to other nearby cells, causing a chain reaction that kills off more cells than the initial injury did," Borgens said. "Until now, the end result has been irreparable damage to the spinal cord, causing partial or complete paralysis."

PEG is able to stop this cascade of injury by repairing initial membrane damage, or by fusing two damaged cells together into a larger functional nerve cell. Significantly, the polymer is attracted only to damaged nerve cells and tissue when it's injected into the blood stream. It doesn't move into undamaged regions nearby.

About five years ago, Borgens and colleague Riyi Shi found that they could fuse hundreds to thousands of severed nerve fibers in a guinea pig spinal cord with just a two-minute PEG treatment. That put them on the path toward using the polymer as a repair agent to mend spinal nerve cells after traumatic injury......

........"More than half the dogs (in the PEG group) in this study were standing or walking within two weeks of treatment," Borgens said. "In most cases, you could notice positive signs within three to five days. These results are unprecedented in paralysis research."      Read More...

Summarizing the abstract in J Neurotrauma. 2004 Aug;21(8):994-1007 resulting from an earlier study, helps to connect some "spaces between the dots" in the seattlepi.com article:

Spinal cord injury (SCI) results in rapid and significant oxidative stress. The above researchers have previously demonstrated that administration of polyethylene glycol (PEG) inhibits oxidative stress using an in vitro model of SCI. In this particular study they tested the effects of PEG in vivo  to elucidate the mechanism of PEG-mediated neuroprotection. They were able to show that a compression injury at T10-11 induced diffusive oxidative stress in crude synaptosomal preparations, correlated with synaptosomal dysfunction and increased intrasynaptosomal calcium.

Administration of PEG immediately post-injury produced a marked decrease in synaptosomal oxidative stress and calcium, associated with an increase in synaptosomal function.

Confocal microscopy using fluorescein conjugated PEG revealed that PEG entered the cells of the injured spinal cord, placing the polymer in a position to directly interact with cellular organelles. PEG attenuates calcium-induced functional compromise of normal spinal cord synaptosomes and mitochondria in vitro. The results indicate that PEG may exert its neuroprotective effect through direct interaction with mitochondria, besides its known ability to rescue neurons and their axons by repairing the plasma membranes.

The researchers postulate that PEG is likely to interfere with the cascade of secondary injury by several mechanisms of action that in concert reduce oxidative stress.  PMID: 15318999

Post Comment: Seventy-five percent of the dogs in the Dec 04 study were able to resume a normal life. If only we knew what evaluative tool(s) were necessary in order to know why twenty-five percent failed to respond. It's the source of a real pain in the neck in science, we only get answers to the questions we ask. But magnum cudos to Borgens and Shi. Their hard work may just lead to a lot of people walking that can't do so now.
 

Posted by Hyscience at December 6, 2004 3:51 PM



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