PORTLAND, Ore. - Stephen A. Back, M.D., Ph.D., an internationally recognized expert in pediatric neurology at Doernbecher Children's Hospital, Oregon Health & Science University, recently was awarded a prestigious $2,346,313 Javits Neuroscience Investigator Award from the National Institute on Disease and Stroke (NINDS) for his pioneering work in the cellular and molecular cause(s) of brain injury in premature infants. NINDS is a branch of the National Institutes of Health.
"I am thrilled the NINDS continues to recognize the potential of the unique research models we have developed - some of which are not used anywhere else in the world. With the help of this long-term grant, we hope to devise therapies that cannot only reverse brain damage in infants but slow cognitive decline in aging adults as well," said Back, associate professor of pediatrics and neurology, Doernbecher Children's Hospital, OHSU School of Medicine.
Back's research looks at the mechanisms responsible for causing white matter brain injury in developing infants. White matter brain injury is the underlying basis for cerebral palsy, or CP, a condition in which permanent brain damage causes movement disorders, including inability to walk without an assistive device, inability to use one's arms and legs and weak torso muscles; as well as, intellectual challenges, including thinking, reasoning, remembering, imagining or learning words.
Premature birth is the leading cause of cerebral palsy, explains Back, and in the United States, a child who will develop CP is born every 30 minutes. In addition, he says, children are 10 times more likely to have CP than cancer.
"Dr. Back's groundbreaking work is increasing our knowledge of what causes cerebral palsy and other important neurological diseases," said Stacy Nicholson, M.D., Doernbecher Physician-in Chief and Credit Unions for Kids Professor and Chair of Pediatrics, OHSU School of Medicine. "His work should lead to real breakthroughs for patients struggling with these debilitating disorders. OHSU and Doernbecher are fortunate to have a scientist of his caliber."
"The Javits Investigator Award for Dr. Back is a recognition of his seminal contributions to the field of developmental brain injury. His proposed work includes the use of a novel pre-clinical animal model to test new translational strategies that will have the potential for restoration of normal myelination and neurological function in children with white matter lesions," said Dan Tagle, Ph.D., program director for Neurogenetics, NINDS, NIH
Back and colleagues hope their research will benefit three large groups of children at risk for CP : infants that survive after premature birth, full-term babies later discovered to have brain injury that occurred during pregnancy; and infants born with heart disease. These infants commonly develop injury to one major part of the brain, called the white matter, which contains the nerve fibers that control brain functions such as walking, speaking and thinking. White matter injury occurs when blood flow to the developing brain falls below normal or when maternal infection occurs during pregnancy. Critically ill premature babies are especially at risk to develop white matter injury from either cause.
White matter injury occurs during brain development when nerve fibers in the white matter are actively being wrapped in myelin, the insulation that allows nerve fibers to rapidly transmit signals in the brain. Dr. Back and his team have shown that during human brain development, there is a critical time period when the cells (oligos or oligodendrocyte progenitors) required to make myelin are easily killed by low blood flow to the brain. The loss of these oligo-cells results in failure to make the myelin required for normal brain function.
Progress in preventing this brain injury has been slow, Back says, because of the lack of animal models to test therapies for the complex forms of brain injury that occur in human survivors of premature birth. Recently, Back's team developed the first animal model that reproduces the major forms of brain damage that occur in premature infants. This model has substantially altered the way leaders in this field believe damage occurs to the developing white matter of the brain.
"We previously believed that the developing brain fails to make normal myelin, because the oligo-cells that make the myelin were completely killed. Hence, it was thought that the children with CP sustain permanent abnormalities in movement and intellect," Back explained. "However, our recent studies suggest that this view may not be correct."
Back and Lawrence Sherman, Ph.D., an associate scientist in the OHSU Oregon National Primate Research Center, have discovered that after adult white matter damage, numerous oligo-cells survive, but fail to mature to make myelin. This appears related to a molecule called hyaluronic acid (HA) that builds up in the damaged white matter and prevents the normal production of myelin.
"The oligo-cells are blocked at a critical period in their cell development before they are able to make myelin. The fact that these cells appear normal and are present in large numbers in the regions of brain damage raises the possibility that we might develop therapies that allow these oligo-cells to mature and make the myelin needed to restore greater function to the damaged brain," Back said.
Back is the second OHSU researcher to receive this highly coveted award. In 2002 Edward Neuwelt, M.D., professor of neurosurgery and neurology, OHSU School of Medicine, Portland Veterans Affairs Medical Center, and director of the OHSU Blood Brain Barrier Program, received a Javits Award for his contributions to the understanding of the blood-brain barrier and his progress toward innovative strategies for treating central nervous system tumors.
"Dr. Back's multidisciplinary laboratory collaborates with leading scientists in academic institutions around the world. This cross-fertilization among scientific leaders is an NIH priority intended to accelerate the pace of translational research. We are delighted his work has been singled out by this very senior assembly of distinguished neurologists and neuroscientists," said Mark Richardson, M.D., M.B.A., dean, OHSU School of Medicine.