Discovery by U of S Researchers May Help Prevent Paraplegia

Posted March 09, 2001


FOR IMMEDIATE RELEASE ? 10 a.m. Friday, March 9, 2001 2001-03-05-ME

Discovery by U of S Researchers May Help Prevent Paraplegia

In a just-published article, University of Saskatchewan researchers have
shown that a new drug is effective in preventing paraplegia in rats with
spinal cord injuries. Human clinical trials of this promising treatment are
expected to begin in a year or two.

"If it works as effectively in humans as in rats, it should greatly reduce
the devastating effects of spinal cord injury," says Bernhard Juurlink, head
of the department of anatomy and cell biology and leader of the team working
on the new treatment.

The team?s findings were recently published in the prestigious Federation of
American Societies for Experimental Biology (FASEB) Journal.

Every year more than 1,000 Canadians sustain spinal cord injuries that cause
permanent damage. including paraplegia and quadraplegia.

Juurlink notes that the body?s response to spinal cord injury causes
oxidative stress (increased levels of very reactive oxygen). This starts a
chain reaction leading to inflammation that can do as much damage as the
initial injury. Preventing oxidative stress and inflammation from damaging
the spinal cord is more effective than trying to repair the damage after it
has been done, he says.

Along with neurosurgeon Robert Griebel, pharmacy professor Phyllis Paterson,
post-doctoral fellow Huse Kamencic and clinical research fellow Elisabeth
Sch? Juurlink is investigating methods of reducing oxidative stress in
the spinal cord by administering a compound known as
L-2-oxothiazolidine-4-carboxylate or OTC soon after injury.

The drug methylprednisolone is currently used to reduce secondary damage
after spinal cord injuries, but OTC stops the chain reaction leading to
oxidative stress earlier than does methylprednisolone, and so appears to be
more effective.

The team has shown that in rats, OTC greatly decreases oxidative stress in
the injured tissue, resulting in greatly reduced secondary damage. With OTC
treatment, animals with injuries that would normally cause paralysis can
walk.

The study concludes that since the rats show "significant retention of
function", this may be an effective treatment for spinal cord injury in
humans. The central nervous system is basically the same in all mammals, so
the positive results in animal trials are promising.

But Juurlink cautions, "There are a lot of drugs that work in rats that
don?t necessarily work in people." For example, drugs need to move from the
bloodstream into the brain and spinal cord in order to combat oxidative
stress, but a drug that crosses the blood-brain barrier in rats may not do
so in humans.

The Saskatchewan Neurotrauma Initiative is currently funding his spinal cord
injury research. Juurlink also receives funding from the Regional
Partnership Program, a jointly funded initiative of the Canadian Institutes
of Health Research and the Saskatchewan government.

Further research still needs to be done to determine the appropriate dosage
of OTC and how soon after injury it needs to be given.

For the initial experiment, the rats were given OTC 30 minutes after the
injury. Juurlink says he suspects OTC is most effective if given within
three hours, and has some positive effect if given up to 24 hours after
injury. This is the ?therapeutic window? during which methylprednisolone is
effective in reducing oxidative stress.

Because OTC has already been used in treating other problems such as
respiratory distress and ALS, it is likely that clinical trials can begin
relatively quickly, said Juurlink.

For more examples of how U of S researchers are helping to unravel the
mysteries of the brain and the nervous system, attend "Brain Show 2001"
Sunday, March 18 at City Hospital. The event is organized by the
Saskatchewan Neuroscience Network.

Kathryn Warden
Research Communications Officer
University of Saskatchewan
Tel: (306) 966-2506
Fax: (306) 966-2411
kathryn.warden@usask.ca
http://www.usask.ca/research

Bernhard Juurlink
Head of the Department of Anatomy and Cell Biology
University of Saskatchewan
Tel: (306) 966-4083
Fax: (306) 966-4298
Juurlink@duke.usask.ca