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Key advance reported in regenerating nerve fibers

BOSTON -- Researchers at Children's Hospital Boston and Harvard Medical School have advanced a decades-old quest to get injured nerves to regenerate. By combining two strategies activating nerve cells' natural growth state and using gene therapy to mute the effects of growth-inhibiting factors they achieved about three times more regeneration of nerve fibers than previously attained.

The study involved the optic nerve, which connects nerve cells in the retina with visual centers in the brain, but the Children's team has already begun to extend the approach to nerves damaged by spinal cord injury, stroke, and certain neurodegenerative diseases. Results appear in the February 18th Journal of Neuroscience.

Normally, injured nerve fibers, known as axons, can't regenerate. Axons conduct impulses away from the body of the nerve cell, forming connections with other nerve cells or with muscles. One reason axons can't regenerate has been known for about 15 years: Several proteins in the myelin, an insulating sheath wrapped around the axons, strongly suppress growth. Over the past two years, researchers have developed techniques that disable the inhibitory action of myelin proteins, but this approach by itself has produced relatively little axon growth.

The Children's Hospital team, led by Dr. Larry Benowitz, director of Neuroscience Research, reasoned that blocking inhibition alone would be like trying to drive a car only by taking a foot off the brake. "Our idea was to step on the gas to activate the growth state at the same time," Benowitz said. "Knocking out inhibitory molecules alone is not enough, because the nerve cells themselves are still in a sluggish state."

The researchers injured the optic nerves of rats, then used a two-pronged approach to get the axons to regenerate. To gas up the sluggish nerve cells, Dr. Dietmar Fischer, first author of the study, caused an inflammatory reaction by deliberately injuring
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Contact: Aaron Patnode
aaron.patnode@childrens.harvard.edu
617-355-5337
Children's Hospital Boston
17-Feb-2004


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