For just a moment, allow the science of today to become the reality of tomorrow.
A professional football player suits up for a Sunday night football game—donning pads, shoes, jersey and of course, to protect himself from concussion, his helmet. Then, as part of his regular routine, he takes one single pill—a pill that could do more to protect his brain from long-term damage from concussion than the best-designed helmet ever could.
Consider another scenario. A young soldier in an armored vehicle travels along a dusty desert road in a war zone. Suddenly, an improvised explosive device (IED) explodes, flipping the vehicle. The blast sends him spinning into the air and crashing to the ground. Within minutes, a fellow soldier injects him with a drug that will protect his brain from the devastating effects of a traumatic brain injury (TBI).
These two scenarios may seem futuristic, but the research behind them is going on right now in the CU School of Medicine Pharmacology Department in the laboratory of Kim Heidenreich, PhD.
“It is so exciting to actually see your research have the potential to help society,” said Heidenreich. “It’s also a thrill to train young scientists who are so excited about what we are doing.”
One second—a lifetime of consequences
At least 1.7 million American civilians suffer a TBI each year, most frequently from motor vehicle accidents, falls and sports injuries. As much as 20 percent of the 2.3 million troops deployed to Iraq and Afghanistan since 2001 have suffered a TBI after exposure to an IED. Although the initial injury might just take a second, the brain damage resulting from a TBI evolves over time—hours, days, years or a lifetime—and extends beyond the initial site of injury.
The multiple events that occur after the initial injury—including inflammation, brain swelling and death of brain cells—are collectively referred to as secondary brain injury. Secondary brain injury can lead to death and ultimately contributes to long-term physical, cognitive, behavioral and emotional impairments months to years after the TBI. TBI is known to increase the risk of developing epilepsy and Alzheimer’s disease (AD). More recently, there is evidence that repetitive TBI is associated with chronic traumatic encephalopathy, a neurodegenerative disorder with similarities to AD.
What if early intervention could minimize the consequences of secondary injury? In the past decades, clinical trials of potential treatments for secondary brain injury have left researchers disillusioned. But Heidenreich frequently uses the word “exciting” when she talks about a class of drugs called FLAP (5-Lipoxygenase-activating protein) inhibitors, which are being developed for use in treating asthma but might also be used either before or after a TBI to mitigate the seriousness of secondary injury.
A Eureka moment
Heidenreich traces her current research back to a Eureka moment when a former graduate student, co-mentored with Robert Murphy, PhD, was investigating whether leukotrienes (small lipid molecules that contribute to inflammatory reactions in different parts of the body, including the lungs) could be made in the brain.
“The student discovered that an uninjured brain has no leukotrienes,” said Heidenreich, “but once the brain was injured and white blood cells infiltrated the brain, sure enough, the brain made leukotrienes.”
The next step was to figure out a way to block the leukotrienes from being created after a TBI. Researchers were already doing clinical trials with FLAP inhibitors to block leukotrienes during asthma attacks. Heidenreich’s research shows that the same class of drugs when administered before or after a TBI blocks leukotriene production and decreases secondary brain injury after TBI.
In short, treatments already being developed for asthma could lead to improved outcomes for victims of TBI.
Too simple?
To those who might think that it’s just too simplistic to think that individuals at high risk for TBI could take a preventive pill, Heidenreich has a straightforward answer: “The simplicity of the approach may, in fact, contribute to its success.”
So Heidenreich—who has already received funding from the CU School of Medicine Center for NeuroScience and from the Colorado TBI Trust Fund—is seeking funding and approval to take her TBI research to the next step: clinical trials. She is also talking with the United States Department of Defense about the implications that her research could have for active members of the military who are exposed to frequent explosions.
Meanwhile, she envisions a day when the devastating results of TBI might be mitigated by prevention and early intervention—with a simple pill or injection.
