22 April 2010

Drug could stop spinal injuries

Shutting off a single gene can help stop the cascade of damage that can paralyse people with spinal cord injuries.

Shutting off a single gene can help stop the cascade of damage that can paralyse people with spinal cord injuries, US researchers reported on Wednesday.

They propose using a common, generic diabetes drug in combination with a gene-silencing technique to stop spine injuries from getting any worse, and believe the approach may also work in people with stroke and traumatic brain injuries.

Their experiment, published in the journal Science Translational Medicine, shows it is possible to stop the bleeding that can cause the damage from an injured spinal cord to spread and worsen.

"What we're doing is preventing bleeding from occurring," said Marc Simard of the University of Maryland, which has licensed the technology to a company Simard works with called Remedy Pharmaceuticals.

Inflammatory factors

When the spinal cord or brain is injured, the capillaries can burst, bringing in an overwhelming wave of chemicals called inflammatory factors that are meant to heal, but that often increase the damage. This is why stroke patients do not always show immediate symptoms but can worsen in the hours afterwards.

Simard's team demonstrated that a gene called ABCC8 starts this process. It controls a molecule called the sulfonylurea receptor 1 or SUR1.

"It gets activated after an injury like ischaemia (when blood vessels are blocked) or trauma," Simard said.

Simard's team blocked this gene in mice and rats using gene-blocking therapy called antisense and showed that after a spinal cord injury, the damage and effects were much less without ABCC8.

They also tested the spinal cords of seven patients who died within five days of a spinal cord injury and showed the same gene was active. The next step is to try this approach in people, said Simard.

"I think we are pretty darn close to a clinical trial," he said in a telephone interview.

Easy to make

The antisense drugs are easy to make, he said. And the common diabetes drug glyburide blocks the destructive SUR1 protein made by the gene.

Remedy Pharmaceuticals is working to make an infused version of both drugs that could work together to block the gene and block the protein that the gene makes.

Glyburide is already in Phase I safety trials for treating traumatic brain injury and stroke, Simard said.

"My hope is eventually you could get it into the ambulance," Simard added. He hopes there will be no side-effects from giving the drug, even to lightly injured people, so that ambulance workers could give an immediate infusion to anyone with apparent brain or spinal cord damage to stop the deadly cascade of damage.

Large market

The potential market is large. "Worldwide, the incidence of spinal cord injury ranges from 10 to 83 per million people per year," Simard's team wrote.

Many teams are looking for ways to prevent the early damage that makes brain and spinal cord injuries so devastating.

A team has engineered an enzyme that can gobble up scar tissue formed after spinal cord injuries, and is working with Acorda Therapeutics to develop it.

Another team found last year that injecting tiny polymer spheres into rats right after spine injuries helped the animals recover movement and prevented secondary nerve damage.

Yet another group found last year that a common and safe blue food dye might block inflammation. - (Maggie Fox/Reuters Health, April 2010)

SOURCE: Science Translational Medicine 2010.


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