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Neural Stem Cell Study Arose From Culture of Collaboration

October 10, 2012
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David Rowitch, MD, PhD

A new study that represents a significant first step in exploring the potential of stem cells to treat neurological disease is a "natural outgrowth" of a longstanding culture of interdisciplinary collaboration in UCSF neonatology — a culture that UCSF Benioff Children's Hospital physicians Dr. David Rowitch and Dr. Donna Ferriero work hard to advance.

Rowitch, chief of neonatology at UCSF Benioff Children's Hospital, led a Phase I clinical trial that found the first peer-reviewed evidence that transplanting neural stem cells into the brains of patients is safe, and that the cells engrafted and appear to produce myelin.

The study is just the latest in a number of collaborations led by Rowitch, also a UCSF professor of pediatrics and neurological surgery and a Howard Hughes Medical Institute Investigator, and Ferriero, chair of pediatrics and physician-in-chief at UCSF Benioff Children's Hospital and one of the leading neonatal neurologists in the United States.

The two partner on a number of interrelated enterprises centered on finding causes and developing new treatments for neurological injuries and illnesses in infants: the Newborn Brain Research Institute (NBRI), which Rowitch and Ferriero co-direct; the Neurointensive Care Nursery, where many clinical research protocols developed at NBRI are carried out; the Neonatal Brain Disorders Lab, directed by Ferriero; and the Fetal Treatment Center, directed by Dr. Michael R. Harrison, a pioneer in fetal surgery.

"Donna and David are a dream team," said Dr. Sam Hawgood, dean of the UCSF School of Medicine and vice chancellor for medical affairs. "Both have incredibly strong credentials in basic science, and both are superb clinicians. What they've done is created a new organizational paradigm to focus on the neurology of newborns." Ferriero cited the value of their teamwork.

Donna Ferriero, MD

"Our research has flourished because of collaboration, and ultimately, so has the care we provide as well," Ferriero said, pointing to a slew of recent and ongoing research efforts in neonatal neurology:

  • Management of Myelomeningocele Study (MOMS): This multi-center trial, led by Dr. Diana Farmer, former surgeon-in-chief of UCSF Benioff Children's Hospital, demonstrated that babies who undergo an operation to repair the birth defect spina bifida while still in the womb develop better and experience fewer neurologic complications than babies who have corrective surgery after birth. The trial was stopped early because the prenatal surgery results were so positive.
  • Hypothermia for newborn brains: Under a clinical research protocol, babies with moderate neonatal brain asphyxia — a shortage of oxygen at birth — are being cooled to several degrees below normal body temperature, based on evidence that such treatment can help reduce neurological damage. "We have cooled more than 200 babies so far," said Ferriero. "This is a joint effort run by the Neurointensive Care Nursery (NICN), which harnesses the resources of neurology, radiology, pediatrics and especially the NICN nurses."
  • Planned treatment trial for newborn brain asphyxia: "We have submitted a Phase III trial, based on our completed pilot study, which showed safety. This could not have been done without the collaboration of everyone at NBRI."
  • MRI-compatible incubator: In order to use magnetic resonance imaging (MRI) to monitor brain structure and function in extremely premature infants, a UCSF team led by neonatal neuroradiologist Dr. A. James Barkovich developed the first MRI-compatible incubator — "the prototype for all such devices," noted Ferriero.

Revolutionizing Newborn Medicine

Hawgood, who preceded Rowitch as neonatology chief, drew a parallel with the work of Dr. John Clements, UCSF emeritus professor of pulmonary biology and pediatrics. Clements won the Lasker Award and Pollin Prize for his role in the discovery of pulmonary surfactant and its development as a therapy for premature babies with respiratory distress syndrome.

In the late 1950s and early 1960s, Clements "connected a basic science question — why don't our lungs collapse when we breathe out — to a clinical problem: premature babies dying of collapsed lungs," Hawgood said.

Clements' research called for solving "immense technical problems," such as how to measure blood pressure and blood gases in newborns and how to test very small volumes of blood. "The only way to address those problems was to revolutionize the way we thought about newborn medicine and reorganize the care of newborns," Hawgood said.

In response, UCSF established of one of the world's first neonatal intensive care units in 1964.

"From that moment, we've seen it as our responsibility to answer questions, push the field along and look for innovation," Hawgood said. "And that's only going to happen if there's a very tight working relationship between the researchers in the lab and the clinicians on the front line."

Rowitch said the way to motivate such a talented and competitive group to collaborate is to "create opportunities with tangible goals and key infrastructure pieces to make it easier to realize those opportunities. And people get involved and make it their own."

"Collaboration is the secret sauce of UCSF," concluded Hawgood. "We are renowned for entrepreneurial individuals who strike off in completely new scientific directions, and somehow we have coupled that to a sense of tremendous intellectual generosity.

"People are not overly protective of their particular ideas," he continued. "They are very open to having others come in and enhance the idea, think about where it might be applied, and then build the dynamic teams that need to come together to take these ideas, make a connection to a human disease, and look at how that connection can drive innovation in the clinical arena."

About UCSF Medical Center
UCSF Medical Center consistently ranks as one of the top 10 hospitals in the United States. Recognized for innovative treatments, advanced technology, collaboration among health care professionals and scientists, and a highly compassionate patient care team, UCSF Medical Center serves as the academic medical center of the University of California, San Francisco. The medical center's nationally preeminent programs include children's health, the brain and nervous system, organ transplantation, women's health and cancer. It operates as a self-supporting enterprise within UCSF and generates its own revenues to cover the operating costs of providing patient care.

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