Each year, nearly 500,000 children in the U.S. sustain traumatic brain injuries — one of the leading causes of death or long-term neurologic impairments in the young.
The effects of brain injury are devastating and can result in a wide range of functional changes affecting thinking, learning, behavior, emotions, language and sensation. Traumatic brain injury can also cause epilepsy and increase the risk for Alzheimer’s disease, Parkinson’s disease and other later-in-life brain disorders. Although there are treatments for many of these conditions after they occur, there are no specific treatments targeting the mechanisms that cause brain injury.
Mark S. Wainwright, MD, PhD, attending physician in the Division of Neurology at Children’s, is searching for ways to help children affected by traumatic brain injury and those who have suffered brain injury as a result of conditions like stroke and prolonged seizures. By gaining a better understanding of the mechanisms of brain injuries most common in children, Wainwright and his research team hope to discover new treatments to reverse their effects.
Targeting Brain Inflammation
Wainwright, who is also an associate professor of pediatrics, molecular pharmacology and biological chemistry at Northwestern University’s Feinberg School of Medicine, is studying the inflammatory response of the brain resulting from traumatic injury. Research into Alzheimer’s disease has shown that this uncontrolled inflammation can lead to further brain and nervous system injury or the susceptibility to such injury later in life. Wainwright is trying to distinguish the features of inflammation in the brain that repair injury from those that cause injury.
Using animal models, Wainwright and researchers at Northwestern University’s Center for Drug Discovery and Chemical Biology tested a new compound developed at Northwestern called Minozac. It targets the overproduction of inflammatory proteins created as part of the body’s natural defense system. These proteins become over-stimulated by certain diseases and can contribute to their progression. Their findings indicated that Minozac can prevent the decrease in cognitive function, which includes perception, memory and creation of imagery and thinking. The compound might also prevent the increased risk of epilepsy later in life. This exciting discovery may have direct applications in caring for children with traumatic brain injury. Minozac is under further development by a biotechnology company in advance of clinical trials on humans.
“As pediatric neurologists, we think in the long term,” says Wainwright. “If we can identify and treat a disease in childhood, we can prevent that disease in adulthood.”
As both a pediatric specialist who treats patients and a researcher in neurobiology, Wainwright concentrates on translational research, which brings the latest cures and treatments developed in the laboratory to patients in the hospital. “The focus in my lab is on identifying the mechanisms that can be altered and targeted to improve outcomes,” he says. “I’m very fortunate to be able to conduct studies in the lab that are directly relevant to what I see in the intensive care unit.”
The neurocritical care program is one of several pilot programs to take advantage of XenoBase, a unique bioinformatics system with the capacity to integrate clinical and research data. Thanks to the generous support of donors, Children’s was the first pediatric institution in the nation to acquire XenoBase. Wainwright, a Davee Scholar, says that access to this cutting-edge technology will help accelerate the development of new treatments.
“We generate huge amounts of data every day in terms of lab results and physical exams and until now we haven’t had the tools to use this data,” says Wainwright, who also directs the Center for Interdisciplinary Research in Pediatric Critical Illness and Injury at Children’s Memorial Research Center. “With XenoBase, we have a tool that allows us to integrate this data. It will position us as a leader in using bioinformatics as a research tool.”
The XenoBase system is just one example of the potential for advances in neurobiology research made possible by philanthropic support. Without this support, says Wainwright, much of the work that takes place in his lab and integrated with a tool such as XenoBase would be impossible.
“We are very conscious of the commitment of the people who raise the money to support our work and we take their trust very seriously,” he says. “Thanks to that support, every day I’m challenged to learn something new that will help us make a difference in the lives of the children we treat.”
Neuroprotection and neurocritical care programs and research at Children’s are supported by The Davee Foundation, the Medical Research Institute Council and its Junior Board Foundation and the Lyndsey Whittingham Foundation, among others.
This article first appeared in the Spring 2009 issue of Heroes magazine.