News Room

An increase in multiple gestations has led to more premature, very-low-birthweight infants. While more of these babies are surviving, up to 35 percent are left with brain injuries leading to cerebral palsy and cognitive/behavioral deficits. During the past decade, researchers at Children's have documented a complex web of insults sustained by premature babies' brain cells, particularly the cells that form the brain's white matter, known as oligodendrocytes. Hypoxia-ischemia, a compromise of the brain's blood and oxygen supply, is often the trigger. Not only are preemies at high risk for hypoxia-ischemia, but their immature oligodendrocytes are exquisitely vulnerable to hypoxic-ischemic injury because of the developing cells' unique biology.

Now, in the June 25 issue of the Journal of Neuroscience, Frances Jensen, MD, Simon Manning, MD, Delia Talos, MD, and colleagues in Children's Department of Neurology and Neurobiology Program demonstrate that the Alzheimer's drug memantine can reduce white-matter injury after a hypoxic-ischemic episode. The drug, marketed in the U.S. as Namenda®, acts by blocking a type of glutamate receptor in the brain known as the NMDA receptor.

Frances Jensen, MD

"The premature brain is not just a 'small' adult brain -- it is physiologically different and thus contains unique targets for therapy," says Jensen, the study's senior investigator. "The NMDA receptor in white matter may be one of those targets. We tested this target in the animal model, and we also show that it is present in the premature human brain."

The next step is to evaluate potential safety risks of memantine in premature newborns. Eventually, Jensen and colleagues hope to conduct a clinical trial in premature infants at risk for PVL.

In 2004, Jensen showed that another type of glutamate receptor, known as the AMPA receptor, is also abundant in developing oligodendrocytes, and that an existing drug for epilepsy, topiramate, can block AMPA receptor activation and reduce the risk for PVL. Jensen hopes to conduct clinical trials of topiramate in newborns and infants, since it is currently FDA-approved only for adults and children over age 3. Since it is only available in oral form, researchers are working on developing an intravenous formulation that could be used in premature infants.

The memantine study was supported by the National Institutes of Health and the William Randolph Hearst Foundation.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.