Scientists Developing Ways to Enhance Nerve Regeneration - 2002-04-27

Scientists already know how to make injured or severed nerve cells, neurons, regenerate and resume carrying messages from the brain to other parts of the body. But, as Johns Hopkins researcher Ronald Schnaar explains, not all nerve cells respond to such treatment.

"Many people have heard of people who have had, say, a finger severed and sewn back on. They regain feeling and movement of that finger. That finger is served by motor neurons that actually start in the central nervous system and reach all the way down to your finger," he explained. "So that the end of the neuron can regenerate just fine over several centimeters in your finger. But if you were to cut that same nerve in the central nervous system, it would not regrow at all."

Professor Schnarr who led the research on new nerve regeneration techniques said we can best understand the nervous system if we think of the electrical wiring of a house. Insulated copper wires carry electricity to a light bulb or a radio, for example. If the wire is cut, the light goes out and the radio stops playing.

"The nerve cells have a cell body and then they have a long extension, axons, which connect to other nerve cells. The axon carries electrical impulses between nerve cells, or between nerve cells and target cells like muscles, and that's how the nervous system works. Those axons must be able to send electrical signals quickly from place to place. To do this, they are wrapped in insulation, called myelin. If the myelin is lost, their ability to signal is lost," he said.

Nerve cells, like other cells of the body, are capable of regeneration. Professor Schnaar said that in many parts the body, damaged axons can and do regrow and re-establish contact with each other. But in the central nervous system, which is an extension of the brain into the spinal cord, the healing process goes awry when an axon is cut or injured. The damaged myelin around the axon, in effect, orders the nerve cell not to regenerate. Professor Schnaar and his colleagues now believe they can reverse this anti-healing biochemical signal.

"Let's take the same analogy. If you were to cut the wire leading from your fuse box to your lamp, your light will go out. If that wire had the ability to grow back into your lamp, the light would go back on. But the insulation that's sitting there is actually stopping the wire from regrowing. That's what this is about," Professor Schnaar explained.

When the insulation, the myelin, breaks down in the peripheral nerves, such as those controlling our fingers, it is quickly removed by cells called macrophages that go in and just gobble up all that debris, leaving the way clear for the nerve cells and their myelin sheaths to regenerate. In the densely-packed central nervous system, however, this process of trash removal and regeneration is very slow.

"But the field has come a long way in the last decade and there is now hope that through understanding all the different ways in which axons are inhibited from regenerating, we can combine technologies and find ways to enhance nerve regeneration in the future. We have demonstrated that particular molecules on the nerve cell surface, called gangliosides, are involved in signals that the nerve cells receive that limit their ability to regenerate," he said.

Professor Schnaar has demonstrated in the test tube that it is possible to remove these blocking molecules, thus restoring the ability of the nerve cells to communicate with each other and start growing again.

"It's worked in the laboratory. The challenge that we are now facing is to test whether it will work in animals," Professor Schnarr said.

The animal experiments will mark the turning point from basic science to eventual human trials. Professor Curtis Fred Brewer of the Albert Einstein College of Medicine, who has collaborated with Professor Schnaar on the nerve regeneration studies, said he is excited about the next stage of research.

"The significance is the potential ability to take these basic science observations of the myelin binding protein and to translate that somehow into nerve regeneration. I think the first steps for any significant clinical progress in this area is to understand some of the molecular properties of the components that regulate nerve growth. Certainly, Dr. Schnaar's work in this area is providing very important new leads that are very exciting," Professor Brewer said.

Ultimately, the scientists hope that they can take what is being learned in Ronald Schnaar's laboratory and develop new drugs that control nerve growth, repair spinal cord injuries and one day permit full recovery for paralyzed accident victims.