CSU center working on brain trauma prevention

FORT COLLINS – Injuries sustained by everyone from infants to soldiers could one day be much less traumatic, thanks to research being conducted with the help of the Colorado Center for Drug Discovery, a state-funded program located at Colorado State University.

The drug research center, or C2D2, has developed preliminary compounds that could lessen the impact of traumatic brain injury, or TBI. Such injuries have become a hot topic nationwide because of their increasing prevalence among veterans and professional athletes.

An initial injury can occur in an instant, when an improvised explosive device detonates in Iraq or a National Football League player sustains a particularly hard hit, but the effects are felt long after the injury is suffered.

Swelling in the brain, death of brain cells and inflammation – collectively known as secondary brain injury – all are potential problems for someone with TBI. If the secondary injury is severe enough, it can cause cognitive, behavioral or emotional impairments or can ultimately lead to death.

In 2010, 2.5 million instances of TBI were recorded in the United States, according to the Centers for Disease Control and Prevention, and about 20 percent of the troops deployed to Iraq and Afghanistan since 2001 have suffered a traumatic brain injury.

But a 2009 breakthrough by a University of Colorado-Denver School of Medicine scientist and subsequent work at C2D2 could help future sufferers of TBI avoid these problems.

Kim Heidenreich, a professor of pharmacology at CU’s medical school, discovered that blocking the production of leukotrienes, a type of inflammatory molecule that often is associated with asthma, at the time the initial brain injury is sustained can help prevent secondary injury down the road.

In order to block leukotrienes, a drug containing a protein known as FLAP must be administered either just before or just after brain injury is sustained, said Heidenreich.

That drug is what C2D2 is helping Heidenreich develop, by providing the chemistry needed to supplement the biology done by Heidenreich and her fellow researchers.

The center’s associate director, Greg Miknis, and a team of scientists have identified compounds that have proved effective, opening the door for clinical trials and the long process of getting a drug approved and commercialized.

Heidenreich’s plan is to repurpose drugs developed by pharmaceutical giant Merck & Co. (NYSE: MRK) for treating asthma, which would speed up the drug’s voyage to commercialization. Even so, getting the drug to market will take years.

The compounds that have been formed are “exquisitely potent,” said Miknis, as they must be in order to penetrate the brain.

“The brain is really good at keeping things out,” Miknis said.

The brain’s ability to protect itself also is the reason the drug must be administered at the time of injury.

“There’s a breakdown of the blood-brain barrier when the injury occurs,” Heidenreich said. That lowering of the brain’s defense system allows the drugs to make their way to the brain.

“But the window does close at some point,” she said.

More funding needs to be found to continue developing the drug, Heidenreich said. Money for TBI research is hard to come by, and C2D2’s grant funding is set to run out in 2016.

The center was initially funded in 2009 through a state initiative meant to promote economic growth through bioscience infrastructure development. The five-year, $2.5 million Bioscience Discovery Evaluation Grant from the state got the center started, and an additional $750,000 in grants from the Office of Economic Development and International Trade’s Bioscience Discovery Evaluation Grant Program will keep money in C2D2’s coffers until 2016.

Finding money beyond that could prove challenging, said Miknis, because federal funding has been cut dramatically and the state program developed in 2009 that initially funded the center is now being applied to all advanced industries in Colorado rather than just bioscience, which means more competition for grant dollars.

The center needs to develop a better business model in order to become sustainable, Miknis said, but just what that model should look like is not yet clear.

Ultimately, Miknis hopes that C2D2 will become the state’s drug discovery center, helping researchers from across Colorado turn their discoveries into drugs that can help treat and prevent conditions of all kinds.

Molly Armbrister can be reached at 970-232-3129, 303-630-1969 or marmbrister@bizwestmedia.com. Follow her on Twitter at @marmbristerBW.


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