Myelin and Spinal Cord Repair
Reprinted with permission from Brain Briefings a publication of the Society for Neuroscience, November 2001
Donald L. Price, M.D., President The Johns Hopkins
University School Of Medicine Fred H. Gage, Ph.D., President-Elect
The Salk Institute Dennis W. Choi, M.D., Ph.D., Past President Washington University

After an unexpected detour on Saturday's bike ride, the gouged skin on your knee easily repairs itself. No such luck for your damaged spinal cord.

In the cord, thin fibers, called axons, extend from nerve cells and normally act as connecting cables, carrying messages from one nerve cell to another. Your ability to function stems from this communication circuit that transfers signals back and forth between the brain and spinal cord to the rest of the body. Once injured, however, unlike many other body components, axons in the adult spinal cord and brain cannot adequately repair themselves. Communication becomes permanently impaired and problems erupt.
For some 250,000 Americans with spinal cord injuries this typically means permanent paralysis, the inability to move or a loss of sensation.

For years, scientists have searched to understand why these axons refuse to regrow. Now, increasing research finds that a fatty sheath, termed eyelid, which wraps around axons, is at least partly to blame. The new data is leading to:

• Clearer insight into the complex biology of axon regeneration.
• New ideas on how to prompt axons to regenerate after an injury.

In the past, myelin was known solely for its positive attributes, such as its ability to speed up the transmission of messages along the axon. But then in the 1980s, researchers found that myelin in the brain and spinal cord also gets in the way of axon regeneration. First, scientists prompted some axons to regrow in a culture dish by tinkering around with their environment. When they added myelin to the picture, however, the growth stopped.

Since that time, research has confirmed myelin's blocking role by showing that interfering with its effects can aid axon repair and restore some function in rodents with spinal cord injuries. For example, a vaccine that initiated a multi-pronged attack against myelin prompted axons to regrow over the animals injuries. Furthermore, treated animals regained some movement in their hind legs, which indicates that the myelin attack reestablished the nerve cells severed communication lines.

This method, however, may have a downside. Possibly it could wipe out too much myelin and trigger nasty side effects. In fact, multiple sclerosis, a disease marked by movement problems, is thought to stem from an internal attack against eyelid. Researchers are currently refining the vaccine and testing it on a group of rodents prone to multiple sclerosis to ensure that it does not cause the disease. They also have identified specific molecules that can signal cells called macrophages to ingest and remove myelin from the damaged spinal cord. By finding ways to solely activate these molecules, they may be able to create a more controlled myelin onslaught.

Other groups are investigating ways to target specific components of eyelid, instead of the entire sheath. In recent years, work identified a clutch of molecules in muslin that contribute to its growth-inhibiting effects. One of these, cutely named Nogo, is under intense investigation. Researchers have developed proteins known as anti-bodies that appear to deactivate Nogo and modestly aid axon re-growth and movement in spinal cord-injured rodents. Currently they are refining this antibody approach and will soon test it in monkeys.

Scientists also are looking for other ways to block Nogo's inhibiting effects. One group found an area on the nerve cell, known as a receptor, which detects Nogo and helps it carry out its inhibiting actions. Then recently they identified some proteins that they think may be able to interrupt this mechanism and allow axons to grow. While scientists are a long way off from helping those with paralysis ride their bike or even walk again, the study of myelin is spurring many new ideas on how to repair the damaged spinal cord and restore at least some function.