Tackling Spinal Trauma

By Christine Gorman

IT WAS NOT A CRUNCH OR A MOAN BUT a horrified hush spreading through the crowd that signaled the ghastly instant. On the Astroturf at Giants stadium, Jets defensive lineman Dennis Byrd lay motionless, unable to move his hands or legs. With all the power of his 266 lbs. of hurtling flesh, Byrd had unintentionally rammed his helmeted head into the chest of his 275-lb. teammate Scott Mersereau. The impact crumpled a vertebra in Byrd's neck, crushing part of the underlying spinal cord as well as plunging dagger-like slivers of bone into the soft, vital nerve tissue.

Byrd faces the possibility of permanent paralysis from the chest down. But thanks to recent developments in treating spine injuries, he has a far better chance of retaining some control of his body than he would have if the accident had occurred two or three years ago. Within hours of his injury, the football player received two new treatments -- one of them not yet approved in the U.S. -- that could help limit the damage. Although the drugs cannot cure paralysis, they may conserve enough nerve function to make the difference between confinement to a wheelchair and being able to walk with braces and crutches.

Spinal-cord injuries, which afflict 10,000 Americans each year, were until recently considered untreatable. But researchers have begun to unlock the secrets of nerve growth and regeneration, and are even talking, in very cautious tones, about the possibility of reversing paralysis. "There are potent new tools that could change the extreme statements often made by physicians, such as 'You'll never walk again,' " says Dr. Richard Bunge, scientific director of the Miami Project to Cure Paralysis. "That may all change -- maybe not within this decade, but certainly within the next."

The first breakthrough occurred when neurologists realized that damage to the spinal cord continues to progress for about 48 hours after the initial accident. As the first nerve cells die, they release toxins that attack neighboring cells that have managed to survive. Some of these toxins are renegade oxygen molecules, called free radicals, that eat through cell membranes. The ensuing flood of biochemicals destroys even more nerve cells. The devastation spreads from the gray matter at the center of the cord to the white matter that surrounds it. Ironically, the body's response to injury only makes matters worse. The inflammation of injured tissue chokes off vital blood flow, destroying an even greater number of nerve cells.

If this cascade of events could be interrupted, researchers reasoned, then further paralysis might be prevented. In 1990 Michael Bracken of Yale University and his colleagues showed that large doses of an inexpensive steroid, methylprednisolone, could do the job. Apparently, the drug attaches itself to the oxygen free radicals, preventing them from attacking vulnerable tissue. Bracken's study showed that if administered within eight hours of the accident, methylprednisolone could cut the amount of secondary damage in half, sometimes making the difference between the patient's being able to walk and not.

The drug, which was quickly administered to Byrd, has become a standard treatment for spinal-cord injuries in the U.S., and health authorities are studying proposals that would allow paramedics to inject the steroid at the scene of an accident. Just as important, says Bracken, methylprednisolone has erased the notion that these injuries are hopeless: "It's opened the door to many other studies that may lead to better recovery." Several groups are testing substances that provide the benefits of methylprednisolone without the side effects, which include depressing the immune system.

Byrd's doctors are also treating the athlete with a ganglioside known as GM- 1, which is a molecule that occurs naturally in cell membranes and seems to help nerve cells communicate. Manufactured by an Italian pharmaceutical company, the experimental drug is currently undergoing clinical trials in the U.S. In a small study completed last year, researchers from the Maryland Institute for Emergency Medical Services gave the drug to 34 patients for four weeks after their injury. One year later, seven had improved markedly. The treatment apparently prevented further damage to the white matter in the cord and perhaps may have stimulated nerve repair.

There may even be hope for the estimated 200,000 Americans paralyzed by old injuries. By studying how nerve cells grow during embryonic development, scientists believe that they will one day learn to overcome the spinal cord's stubborn unwillingness to repair even a 1-cm gap in its length (a gap that is nonetheless large enough to paralyze function). Several biotechnology firms have cloned specific chemicals that regulate nerve growth, though none are ready for clinical use.

One of the most promising areas of research involves proteins that actually inhibit nerve growth. These are present in the central nervous systems of mammals but not in fish or salamanders, which are capable of regenerating damaged spinal cords. By blocking these inhibitory proteins with antibodies, Martin Schwab, of the University of Zurich's Institute for Brain Research, has discovered that he can regrow severed nerves in rats. The results are even better when the animals also receive nerve growth factors. "The question," says Schwab, "is whether the restored nerves are functionally meaningful" -- a matter he is studying.

Researchers elsewhere are zeroing in on ways to bridge gaps in nerve tissue. They have succeeded in doing this in rats with grafts of Schwann cells, specialized cells that manufacture nerve growth factors. They serve as a bridge for the remaining nerve cells to cross over and re-establish contact. Other researchers are using fetal tissue for this purpose. Paul Reier of the University of Florida in Gainesville has achieved dramatic results by injecting a soup of fetal nerve cells into the damaged spines of cats. Felines that couldn't walk at all before surgery regained a limited ability to walk. Rejection, says Reier, remains the biggest hurdle.

At the University of Alabama, cellular biologist Eldon Geisert is studying how to break through the scar tissue that forms around a spinal wound. Nerve cells will grow up to a scar but cannot penetrate it. The barrier is impermeable, Geisert discovered, because specialized molecules in the tissue act like Velcro to link the scar cells tightly together. By manufacturing antibodies that loosen these bonds, Geisert believes he can dislodge the scar tissue, clearing the way for severed nerves to re-establish contact.

Although they will probably never make a broken spinal cord as good as new, researchers are encouraged that they have progressed so quickly. "Now you can tell somebody to their face that there are active research programs that are addressing their problem," says San Diego neurosurgeon Fred Gage. That -- along with the remarkable new treatments administered -- will be Dennis Byrd's best hope.

With reporting by Hannah Bloch/New York, Sylvester Monroe/Los Angeles and Dick Thompson/Washington