Feature-Experimental Drug May Be Shot in Dark for Gymnast
Reuters
03-AUG-98
WASHINGTON, Aug 4 (Reuters)- Doctors admit it is a shot in the dark and that
they may never know whether an experimental new drug has actually helped a
paralysed Chinese gymnast.
But they are thrilled to have received government permission to throw the
drug, GM-1 ganglioside, or Sygen, into the mix of therapies they are giving
17-year-old Sang Lan in an effort to give her back the use of her legs.
The Chinese vaulting champion fractured her neck when she fell during a warm-
up routine at the Goodwill Games in New York this month. Her spinal cord was
badly damaged.
Anxious doctors sought, and got, permission from the U.S. Food and Drug
Administration (FDA) to use the drug, which is adapted from a naturally
occurring body chemical but which is not yet approved for use in this country.
They are cautious about their hopes. Spinal cord injuries are notoriously hard
to treat and can either heal spontaneously or leave a person paralysed for
life.
Sang also had an operation in which a metal rod was installed to stabilise her
spine.
``It's hard to say exactly what any of these things mean,'' said Anthony
Angelo, medical director of the Nassau County Medical Centre, where Sang is
being treated. ``If, as we hope, she has a good outcome, we'll be able to say
the overall approach was effective.''
About 10,000 to 12,000 people suffer traumatic spinal cord injuries in the
United States each year, the Silver Spring, Md.-based Spinal Cord Injury
Association (SCIA) says. The problem is that nerve cells in the the spinal
cord are not like other cells, which divide and grow and renew themselves.
HELPING NERVE CELLS REGROW
While scientists now realise that neurons can sometimes regrow, it is at best
at a much slower rate than other types of cells. But it might be possible to
help them along, or at least to prevent permanent damage after an injury.
Several experimental approaches are in the works but Sygen is furthest along
in the pipeline, Bernadette Mauro, director of the SCIA resource centre, said.
Made by privately held Italian pharmaceutical company Fidia Pharmaceutical,
Sygen has been on the market in several countries since at least 1985. Fidia's
American subsidiary, based in Washington, has just completed a five-year U.S.
trial of Sygen in almost 800 patients and is now reviewing results.
``If the study is positive we'll file a new drug application (with the FDA),''
said Roberto Fiorentini, president of Fidia's U.S. unit.
Sang received the drug under the FDA's compassionate use programme, which
allows investigational drugs to be used in life-threatening or emergency
situations.
Former National Football League player Dennis Byrd, who was paralysed after a
collision in a 1992 game, was given Sygen and eventually regained the ability
to walk. He visited Sang in the hospital to encourage her.
The drug uses GM-1 ganglioside, a normal part of a cell's membrane that helps
control cell growth, development and healing following an injury. Researchers
speculate that it can cause nerve endings to regrow when used as a drug.
It is also being tested in Parkinson's patients, who have damage to certain
brain cells.
DOES SUBSTANCE MAKE CELLS REGENERATE?
Gangliosides are superabundant in nerve cells, but whether injecting them can
cause those cells to regenerate is a big question.
``I personally don't think the data is that convincing,'' said Tony Ho, an
assistant professor of neurology at Johns Hopkins University in Baltimore. Ho,
who works with nerve growth factors, said it is more plausible that Sygen has
some neuroprotective effect-- preventing further damage.
In studies, it was given to patients intravenously within the first 72 hours
of injury in the hopes of halting damage. ``If you intervene very quickly, you
might hope to prevent some neurons from dying,'' Fiorentini said.
Then, as with gymnast Sang, the drug is given daily for about 53 days. In
theory, this continuous therapy will stimulate the body's natural healing
process and potentially regenerate nerves.
``There is a repair process that goes on after the injury, which goes on for
months,'' Fiorentini said. ``If you can somewhat help it with some product,
it's worth trying.''
A 1991 study published in the New England Journal of Medicine found that seven
of 17 patients receiving Sygen had major improvements in neurological
function, and more Sygen patients than placebo patients had improved motor
movement. But most of it was in the lower extremities. Upper limb improvement
was the same in both placebo and Sygen patients.
RESULTS OF STUDY QUESTIONED
Some have questioned these results, partly because it was a small study and
partly because all the patients also received methylprednisolone, a steroid
used to decrease swelling in spinal cord injuries. That might make it hard to
tell how much of the improvement was due to Sygen.
Fourteen of the 17 Sygen patients also had surgery to relieve pressure on the
spinal cord.
There are also safety questions. A number of cases of Guillain-Barre syndrome
have been reported in European patients who have taken Sygen. This condition
causes patients to lose the nerve covering and can itself cause paralysis.
Doctors say the publicity surrounding Sang has prompted other patients to ask
for Sygen, and Mauro says she is helping four families get FDA permission to
try it.
Other approaches being tried by doctors elsewhere include transplants of
foetal nerve cells, which maintain their ability to grow and divide, and the
use of certain stem cells, unspecified cells that can develop into nerve
cells.
Last month Israeli and Swedish scientists said they had healed the damaged
spines of rats by injecting immune cells into the area. They believe the
immune system is deliberately blocked from entering the spine and brain, which
makes it nearly impossible for the body to repair injuries there.