An estimated 800,000 people in the United States have cerebral palsy, a neurological disorder that causes permanent loss of muscle coordination beginning early in life. Affected children may also have speech, hearing, and vision problems as well as cognitive impairment. Ongoing care for patients with the disorder—a potential consequence of premature birth—costs nearly $35 billion a year.

"We actually have a higher incidence of cerebral palsy now than in the 1960s, but this disease has sort of fallen off the radar screen," said David Rowitch. "There seems to be an imbalance between the severity of the problem and the lack of research to try to improve outcomes."

Rowitch, Professor of Pediatrics and Neurosurgery at the University of California at San Francisco (UCSF), is a neonatologist who treats premature infants. His laboratory in the UCSF Institute for Regeneration Medicine investigates the biology of stem cells in the brain. He thinks it is time to change the standard of care for patients at high risk of developing cerebral palsy. To accomplish that, he is exploring the basic biology behind the disease and plans to translate that knowledge into treatments that will reach patients more quickly.

"Recent studies reveal that up to 50 percent of babies born between 24 and 26 weeks gestation (about 6 to 6 1/2 months into a pregnancy) will have some degree of cognitive impairment. They're born quite early during a very important period of brain development," said Rowitch. "The field of neonatology has made real advances in treatments supporting heart and lung function, but when it comes to the brain we have no therapy to improve outcomes in babies born at these early stages."

As an HHMI investigator, Rowitch will help establish a unique program at UCSF where newly discovered information about the developing brain and nervous system can be applied to tiny patients. "You really need to have a specialized clinical setting that doesn't yet exist in the field—we'll be the first in the nation. The hope is to do for the brain what we're already doing for the heart and lungs in neonates. What we're going to attempt is to change the standard of care for children at risk for neurological problems."

A significant barrier to improving outcomes and, ultimately, minimizing the occurrence of cerebral palsy is the lack of fundamental understanding of what goes wrong during brain development to cause the disorder. Cerebral palsy is usually attributed to an early episode of brain damage, but evidence from Rowitch's lab suggests that a major contributing factor is inhibition of the mechanisms the brain normally uses to repair itself.

"The textbook model for how the disease develops is probably inaccurate," he said. "We lack understanding of the root causes for the common variants of cerebral palsy observed in premature infants and why the brain fails to undergo repair."

In Rowitch's opinion, building a better basic understanding of the events that lead to cerebral palsy is one of the first steps researchers must take if they hope to reduce the incidence of the condition. In particular, a comprehensive understanding of brain development is required. High on Rowitch's list of priorities is understanding more about the development of glial cells, the cells that make up "white matter" and provide critical support and communication routes for neurons.

"More than 90 percent of the cells in the human brain are glial cells, but they have been neglected in relative terms compared to research on neurons," Rowitch said. "The hope is that by understanding problems that arise as these cells are developing, researchers will be better equipped to influence the neurological complications of premature birth."

Finding effective ways to intervene would have a tremendous impact on patients' lives, said Rowitch, who was recently reminded of this when he met a 20-year-old man with cerebral palsy who had just graduated from college. "Given the spectrum of patients with cerebral palsy, he's doing very well," Rowitch said, but noted that many aspects of daily life remained a struggle. "He can't dress himself," he said. "We must try to improve our outcomes."