Stalking a Killer:
Researcher Targets
Deadly Foe

In his own soft-spoken way, John Keana is an extremely ambitious man. His goal? No less an achievement than stopping the ravages of stroke­the nation's third most prevalent killer­and traumatic head injury. A professor of chemistry at the University of Oregon, Keana uses his thirty years of laboratory experience to design drugs that can stop brain damage before it stops its victims.
"What happens during a stroke or traumatic head injury," Keana explains, "is that brain cells are deprived of oxygen­often by a blood clot or hemorrhage. This wouldn't be so bad if the damage remained localized, but when the smothered cells die they release a substance that overexcites their neighboring cells and causes them to die and release still more of the substance. It's a chain reaction."
This domino effect can continue for hours or even days. As the cell death slowly ripples through an area of the brain, it may lead to widespread paralysis, inability to speak, coma, or death. Each year stroke afflicts 400,000 Americans and kills 150,000.
Doctors tending to stroke and head-trauma victims have few effective options. No existing drug treatments can keep the dominoes from falling.
Keana and his UO research team, working in collaboration with Eckard Weber, a pharmacology professor at the University of California at Irvine, have developed two neuro-protective drugs. The first, called Cerestat, erects a chemical barricade that shields the still-standing dominoes from those that are tumbling.
A second-generation compound, ACEA 1021, works, in essence, by gluing the dominoes in the standing position; that is, once ACEA 1021 is administered, healthy cells are prevented from succumbing to the destructive chain reaction.
Both drugs are currently undergoing U.S. Food and Drug Administration testing.
"FDA testing is an extremely involved set of tests and assessment that usually takes many years and can cost $300 million," Keana says. "The university, of course, has neither the means nor the mission for such an undertaking, so we partner with private corporations, usually early in the research phase."
The UO holds partial patent rights to both Cerestat and ACEA 1021; private companies have signed license agreements for the compounds. Keana points out that research support from out-of-state pharmaceutical corporations is spent in Oregon on equipment, supplies, and the salaries of researchers.
"And, should one of these drugs make its way to market, the university would stand to earn substantial royalties," he notes.
In the meantime, university students are reaping the benefits of Keana's expertise. The lectures for his sophomore organic-chemistry class of 350 students are peppered with his real-world experience in such areas as writing grants, conducting original research, and publishing results in peer-reviewed journals.
Each year a small number of undergraduates work in Keana's laboratories, gaining practical experience in building complex molecules. It was a UO undergraduate who, under Keanašs supervision, first synthesized ACEA 1021.
Even as the first two antistroke drugs are being tested, Keana's research group is at work on a third-generation compound with more specific targeting and action.
"While personal tragedies will still occur, stroke and head injuries will be much less devastating to the population as a whole in five or ten years due to the research that is going on today both here at the UO and elsewhere," he says. "That's a promise."

Back to INQUIRY, Spring 1996

©1996 University of Oregon