Summer 2007

A Home for Pediatric Research

Jennifer Puck, M.D.

Pediatrics can lag behind other areas of medicine when it comes to studies of new medicines and treatments because it's more difficult to carry out clinical trials for infants and children. Yet children can't simply be treated as mini-versions of adults. Children have distinct diseases and responses to therapies that may not emerge in trials conducted solely on adults.

UCSF's Pediatric Clinical Research Center (PCRC) serves as an example of what's possible when children are placed front and center in a research environment. For more than three decades, PCRC investigators have been pioneering ways to improve outcomes for severely ill children — from developing methods to study premature infants to devising breakthrough treatments for pediatric brain tumors. The PCRC's exclusive focus on children offers unique opportunities for researchers, while giving families a chance to participate in cutting-edge therapies.

Freestanding Center

"There are not many freestanding centers like this in the country, and this one has a long and wonderful history of productivity," says Jennifer Puck, M.D., a professor of pediatrics and program director of the PCRC.

PCRC researchers conducted some of the early studies to develop human growth hormone, for instance, and helped lay the groundwork for HIV vaccines and for methods now in use to prevent the transmission of HIV from mothers to their babies.

"I could go through literally every medical subspecialty and pluck out an example" of important research conducted through the PCRC, adds Pediatrics Professor and Diane Wara, M.D., who formerly headed the center and now co-directs several affiliated clinical research centers. Indeed, nearly a dozen medical services conduct research through the PCRC, including oncology, genetics, cardiology, neurology and urology.

Based in UCSF Benioff Children's Hospital, the PCRC consists of five inpatient beds, an outpatient unit, three infusion stations (where blood samples can be drawn or intravenous drugs delivered), a suite for neurodevelopmental exams and a core lab to manage samples. There is also a mobile pediatric research team to conduct bedside research at other sites.

Broad Expertise

To help researchers carry out their protocols — at present, 74 are underway — there is a corps of 11 highly skilled pediatric nurses, as well as neonatal and critical care nurses, who screen patients for studies and work with the families. There are also a biostatistician to help with designing studies and a bionutritionist, as well as computer and administrative support. All are well-versed in the unique requirements of working with children and in providing the warmth and empathy needed by critically ill children and their families.

That expertise is invaluable, says Stephen Gitelman, M.D., director of the UCSF Pediatric Diabetes Program. Gitelman is exploring various ways to "alter the course of type 1 diabetes" at various points in the disease's progression, from prediagnosis to full-blown insulin dependence.

Promising Research

One promising line of research is aimed at extending the "honeymoon phase" in newly diagnosed diabetics, when they still have enough beta cell function to produce some of their insulin. Gitelman is testing monoclonal antibodies and other immunomodulatory drugs that appear to delay destruction of the beta cells. "It would be very hard to do these kinds of studies in a standard hospital ward or an outpatient treatment center," he says.

Another important area of PCRC research is searching for markers in the brain that may portend the neurological problems that often develop in babies born prematurely or with certain congenital disorders. "If we can tell which infants are most at risk for developing problems, then different types of therapies can be initiated," says Pediatrics Professor Ronald Clyman, M.D.

Until recently, imaging studies to identify those markers were out of the question. The infants at risk are typically too sick and unstable to move from intensive care to the MRI suite. Nancy Newton, head of the PCRC neonatal research nurses, helped devise a solution: a mobile incubator that has made it possible to safely transport these fragile infants to the MRI.

Though the research is still in its early days, there have already been some important findings, says Clyman. For instance, it's known that babies with congenital heart disease who undergo pulmonary bypass are at risk for neurological abnormalities later in life. But it's been unclear whether those problems are a result of the disease or the bypass procedure.

Imaging Studies

Imaging studies by PCRC investigators have found brain lesions in those babies before they ever have surgery, suggesting some of the neurological sequelae may be related to their heart condition or to therapies that occurred prior to their surgery. That information, says Clyman, "enables us to talk more intelligently about the risks and advantages of the procedure."

The access to patients made possible through the center has also facilitated valuable longitudinal studies. One recent project by Professor of Epidemiology Thomas Newman, M.D., followed newborns with high bilirubin levels and compared their neurological development with that of control babies. The study, which was published in the New England Journal of Medicine last year, found no significant difference between the two groups after five years, suggesting that hyperbilirubinemia may not be as risky a condition as is widely thought.

"These results are reassuring to parents, and may lead to changes in how these babies are managed," says Wara.

With the establishment of the new NIH-funded UCSF Clinical and Translational Science Institute (CTSI), the PCRC will be folded into a broader, University-wide structure aimed at promoting bench-to-bedside innovations. It's not clear yet how the changes will affect the center, but Puck and Wara say the basic mission will remain the same: to improve basic understanding of pediatric diseases and to speed delivery of promising treatments for patients. After all, as Wara points out, the CTSI "is an extension of what's been going on at the center for over 30 years."

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