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Team Regrows Neurons Controlling Movement in Rats
Date:4/6/2009

Goal is to one day develop a therapy to help with spinal cord injuries

MONDAY, April 6 (HealthDay News) -- Using genetically engineered cells and a virus as a delivery method, researchers were able to regenerate a type of nerve fiber in rat brains that controls movement.

This isn't the first time researchers have shown it's possible to re-grow some neurons responsible for movement. But the new research showed regeneration of a particular type of neuron -- corticospinal motor axons -- that had so far proven resistant to regeneration efforts.

Corticospinal motor axons are key to controlling fine and gross motor skills, including walking, in humans, said senior study author Dr. Mark Tuszynski, a professor of neurosciences and director of the Center for Neural Repair at the University of California, San Diego.

"Previous research has succeeded in regenerating nerve connections that arise from some types of cells affected by a spinal cord injury," Tuszynski said. "However, until now, there has not been success in eliciting the regeneration of injured connections from corticospinal motor axons, cells which are essential to restoring voluntary movement in humans."

While the goal is to eventually repair spinal cord injuries in people, researchers say they have much yet to learn, and a therapy is at least several years away.

The findings were published in the April 6 online edition of the Proceedings of the National Academy of Sciences.

The corticospinal tract is a massive collection of nerve fibers called axons, long slender projections of neurons. The neurons, which run between the brain's cerebral cortex and the spinal cord, carry signals for movement from the brain.

Voluntary movement occurs when upper motor neurons in the frontal lobe of the brain send signals to the lower motor neurons, which in turn send the nerve impulses to the muscles.

In spinal cord injuries, the axons of the corticospinal tract are severed so that the lower motor neurons below the site of injury can't receive those signals from the brain.

There are about 10 classes of cells in the nervous system that generate and control movement in humans. Corticospinal motor axons are a key part. Any therapy to repair nerve damage in spinal cord injuries would likely need to include the corticospinal motor axons, said Jacqueline Bresnahan, an adjunct professor of neurological surgery at the University of California, San Francisco.

"Some regeneration has been shown in prior studies, but not very much," said Bresnahan, who's also chairwoman of the Christopher and Dana Reeve Foundation scientific advisory council. "The importance of this study is they are getting quite a robust response from these cells."

The researchers genetically engineered the corticospinal motor axons in the brains of rats to be more sensitive to brain-derived neurotrophic factor -- natural proteins of the nervous system that stimulate growth of neurons. The cells were re-programmed to produce a receptor for the growth factor.

The genetically engineered cells were delivered to brain lesion sites in the rats. The researchers did not test the functional recovery of the rats, because the animals didn't have a spinal injury.

Still, there are major hurdles to cross before a therapy could be developed that would help people.

The re-grown axons extended into a region of the deep brain but did not extend down the spinal cord, where they would need to go to help people with a spinal cord injury, Tuszynski said.

"The genetic engineering only allowed the growth factor receptor to go part way down the axon. That's what we're working on now -- trying to get the cell to send the receptor down all the way into the spinal cord," he said.

And even if the techniques to regenerate corticospinal cells are perfected, any therapy would probably also need to include other yet-to-be developed treatments.

"At the end of the day, there is a lot of hope, but the therapy will depend on combining several treatments to have the most powerful effect," Tuszynski said. "But we are an important step closer. Without this group of cells regenerating, there was very little hope we could come up with a therapy that would help humans."

More information

The Christopher and Dana Reeve Foundation has more about spinal cord injuries.



SOURCES: Mark Tuszynski, M.D., Ph.D., professor of neurosciences, University of California, San Diego; Jacqueline Bresnahan, Ph.D., adjunct professor of neurological surgery, University of California, San Francisco; April 6, 2009, Proceedings of the National Academy of Sciences, online


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