Stops Pulled on Nerve Regeneration

Published: March 2, 2004  |  Source:

By Gabe Romain, Betterhumans Staff

“Stepping on the gas” could lead to better spinal cord treatments

A two-pronged strategy of enhancing growth and halting growth inhibitors greatly improves the Regeneration of nerve fibers and could lead to new treatments for spinal cord injury and some eye and brain diseases.

By combining the two strategies, researchers at Children’s Hospital Boston and Harvard Medical School in Massachusetts have achieved about three times more regeneration of nerve fibers than previously attained.

“When we combined these two therapies—activating the growth program in nerve cells and overcoming the inhibitory signaling—we got very dramatic regeneration,” says Children’s Hospital researcher Larry Benowitz.

Broken transmission

Nerve fibers, known as axons, are long cellular projections that conduct electrical impulses away from a Neuron’s body.

Axons are the primary transmission lines of the nervous system, and as bundles, they make up nerves.

Normally, axons can’t regenerate because several proteins in Myelin—an electrically insulating fatty layer that surrounds the axons—strongly suppresses cell growth.

Two-pronged strategy

Over the past two years, researchers have developed techniques that disable the inhibitory action of myelin proteins, but such techniques did not make nerves regenerate.

Benowitz and colleagues therefore tried a two-pronged approach to stimulating nerve regrowth, reasoning 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,” says Benowitz. “Knocking out inhibitory molecules alone is not enough, because the nerve cells themselves are still in a sluggish state.”

Stimulating growth

To stimulate optic nerve regrowth in rats, the researchers first had to damage their optic nerves, which stimulated immune cells to travel to the site and release growth factors that repaired the damage.

As Benowitz and colleague had found previously, these growth factors activate genes in the retinal nerve cells, causing new axons to grow in the optic nerve.

To enhance this growth, the researchers used a modified virus to deliver into retinal cells a gene designed to turn off the proteins that are programmed to stop regrowth.

Fine tuning

Although the amount of Axon regeneration wasn’t enough to restore sight, it was about triple that achieved by stimulating growth factors alone, says Benowitz, who, along with his colleagues, will continue studying the optic nerve.

“We have to fine-tune the system, and we have some ideas of how to do it,” says Benowitz.

One big challenge for restoring sight is getting nerve fibers from the eye to hook up to the correct centers in the brain so that images aren’t scrambled.

“It’s a mapping problem,” says Benowitz. “We have to retain the proper organization of fiber projections to the brain.”

The research is reported in the Journal of Neuroscience