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1993-04-08
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MEDICINE, Page 57Tackling Spinal Trauma
After decades of hopelessness, researchers are developing drugs
that limit spinal-cord damage, encourage nerve growth and might
someday even reverse paralysis
By CHRISTINE GORMAN - With reporting by Hannah Bloch/New York,
Sylvester Monroe/Los Angeles and Dick Thompson/Washington
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 meaning ful" -- 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.