Children’s Researchers Find Potential Treatment for White Matter Injury

Friday, January 16, 2015

White matter injury (WMI), one of the most common consequences of premature birth, can produce long-term neurodevelopmental deficits. A study by researchers at Children’s National Health System provided direct evidence that targeting specific receptors in white matter cells after brain injury promotes cellular and functional recovery.

One of the Most Common Consequences of Premature Birth

In the United States, about 500,000 babies are born prematurely each year, with about 2 percent of them born at less than 32 weeks gestation. Up to 90 percent of these children survive, but they often suffer a number of abnormalities, including underdeveloped lungs. Underdeveloped lungs can lead to insufficient oxygen supply or hypoxia, which in turn contributes to WMI. No treatment currently exists to improve function in these infants once injury occurs.

During normal fetal and postnatal development, oligodendrocytes (myelin-producing cells in white matter) arise from oligodendrocyte progenitor cells (OPCs). In premature infants, hypoxia prevents OPCs from maturing properly, and the cells begin to die. Without sufficient myelin, the brain cannot process nerve impulses effectively, leading to significant delays in the development of sensorimotor skills and cognition.

Children's Researchers Study White Matter Injury Treatment Options

“We have only recently begun to understand how hypoxia (insufficient oxygen supply) and related brain injury affect white matter development and myelination in the developing brain,” Vittorio Gallo, PhD, Director of the Center for Neuroscience Research at Children’s National, who led the study, said. “We knew from previous research that the epidermal growth factor receptor (EGFR) plays a significant role in the maturation of oligodendrocyte progenitor cells (OPCs). In this study, we wanted to see if enhanced EGFR signaling could stimulate the OPCs to develop normally.”

The team was able to model premature brain injury and administered the EGFR treatment.

“After treatment, the selectively targeted OPCs were identical to normal, healthy oligodendrocytes,” Joseph Scafidi, DO, pediatric neurologist at Children’s National and the study’s lead author, said.

Due to limited duration of the OPC’s plasticity response, there is a very narrow window of intervention opportunity.

“Treatment must be administered within a week after injury,” Dr. Gallo said. “After that, there’s no effect.”

While the team’s finding, published in Nature, demonstrate that the treatment is clinically feasible and potentially applicable to children with WMI, Dr. Gallo cautions that more research is needed to develop safe and effective therapeutic approaches.

“This study highlights the importance of the brain’s plasticity response,” Dr. Gallo said. “Researchers need to take full advantage of that response for therapeutic purposes.”

Find this article and others in Advancing Pediatrics, quarterly publication.


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