CHOC Stem Cell Production Facility to Accelerate Research into Rare Neurological Diseases

StemCellLabpicCHOC’s new stem cell production facility, slated to open late this summer, will allow CHOC researchers to produce patient-specific cells for immune-matching therapies that could positively impact fatal neurological diseases in children – all at a fraction of the cost of building a larger, more complex laboratory.

Within the state-the-art softwall clean room, CHOC researchers will study a stem cell-based therapy for the treatment for mucopolysaccharidosis (MPS-1), a rare and progressive neurodegenerative disease that typically claims patients before they reach the age of 10.

“Based on the results of animal trials we’ve conducted so far, we have a high degree of confidence that stem cell-based therapy will work to treat MPS-1,” said Philip Schwartz, Ph.D., senior scientist at the CHOC Research Institute and managing director of the National Human Neural Stem Cell Resource.

“If our research is successful, the approach could be used to treat a number of other immune-based diseases that damage the nervous system, like multiple sclerosis,” Dr. Schwartz said.

The approach involves using umbilical cord blood to replace a patient’s immune system, then implanting neural cells derived from the same blood into the brain to repair and prevent brain damage.

While implanting cells directly into the brain isn’t new, current treatment protocols require that patients take immunosuppressant drugs to reduce the risk of rejection, which leaves them vulnerable to a host of infections. Standard procedures for replacing the immune system, like bone marrow transplants, aren’t effective for patients with brain disorders caused by their underlying disease because the transplanted cells don’t cross the blood-brain barrier and therefore don’t slow the progression of brain disease.

The new facility will be one of less than a dozen in the nation and the only one that is focused on immune matching rather than immune suppression.

Dr. Schwartz estimated that it would require about five years of work to establish a program before approaching the U.S. Food and Drug Administration for approval to begin Phase I clinical trials. The current research project is supported by a $4.27 million grant from the California Institute for Regenerative Medicine.

Dr. Philip Schwartz Discusses Autism Research

Researchers are studying autism, a brain disease, by turning skin cells into brain cells through genetic manipulation, Philip Schwartz, Ph.D., a senior scientist at CHOC Research Institute, tells “American Health Journal.”

Scientists are using these cells with a goal to develop drug therapies for autism, as well as a diagnostic tool for the disorder, Dr. Schwartz says.

Learn more about autism research in “American Health Journal,” a television program that airs on PBS and other national network affiliates that reach more than 30 million households.

Each 30-minute episode features six segments with a diverse range of medical specialists discussing a full spectrum of health topics. For more information, visit www.discoverhealth.tv.

Philip Schwartz, Ph.D., is nationally recognized for his research in the stem cell field. His research focuses on the use of stem cells to understand the neurobiological causes of autism and other neurodevelopmental disorders. With funding support from CHOC, Dr. Schwartz established the National Human Neural Stem Cell Resource (NHNSCR) in 2001 to support national research in the field of neural stem cells by providing a reliable source for these cells to investigators nationwide

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New Technique Reduces Post-Surgery Pain in Children

CHOC researchers have identified a new technique that significantly decreases pain and the need for pain medication in children following high-risk urology surgeries, a finding that was recently published in the “Journal of Pediatric Urology.”_MG_7464_1

“While pain management is a fundamental part of pediatric surgical recovery and care for pediatric patients, current options involve strong prescription painkillers that can put patients at risk for adverse side effects and possible complications,” said Antoine E. Khoury, M.D., urology chief at CHOC and a study investigator. “This study demonstrates a major advancement in pain management for pediatric urology patients, significantly reducing postoperative pain and the need for pain medicine.”

The research team evaluated the continuous infusion of local anesthesia using a pump pain relief system commonly used in adults to improve pain control in children who have undergone urological procedures. While the ON-Q system is well-established as an effective pain management technique for adults, this is the first study that evaluates its pain management effectiveness in children.

Published in December 2013, the study found that the ON-Q pump system decreased the amount of pain experienced by children on the first and second postoperative days, and that it significantly reduced the need for narcotics.

Because the device delivers the anesthetic in an automatic continuous drip, patients and their caregivers don’t need to adjust the dosage. It is also contained in a pouch, allowing children to move freely during recovery.

During the study, nurses assessed patients’ pain using the Visual Analog Scale (VAS) and the Face, Legs, Activity, Cry, Consolability (FLACC) scale, depending on the child’s age, for both the test group and a control group, which received standard-of-care pain management.

Researchers recommend conducting additional clinical studies to further validate this technique as a superior option for postoperative pain management in children undergoing surgery.

In addition to Dr. Khoury, authors for the research study, “Application of continuous incisional infusion of local anesthetic after major pediatric urological surgery,” include Guy Hidas, Hak J. Lee, Blake Watts, Maryellen Pribish, Edwin T. Tan and Zeev N. Kain.

Curiosity Drives Infectious Diseases Research

A CHOC investigator-initiated trial into neonates with necrotizing enterocolitis (NEC) has discovered key microbial and survival differences in patients who develop blood stream infections. These findings may help explain why premature infants with intestinal pathology experience more complications and higher mortality rates. CHOC Infectious Diseases Medical Director Antonio Arrieta, M.D., and his team have also described better outcome of bacteremia in full-term neonates when it is associated with urinary tract infections (UTI). This, they hope, will lead to changes in how both populations are managed.

Dr. Arrieta and CHOC Resident Jordan Fisher, M.D., presented their UTI data in November 2011 at the World Society of Pediatric Diseases in Melbourne. In May 2012, the data on NEC was presented to the European Society for Pediatric Infectious Diseases in Greece.

These are two of the many investigatorinitiated research trials Dr. Arrieta and his team conduct with CHOC residents to answer questions they hope will ultimately impact children everywhere.

“Our investigator-initiated trials are a small portion of the total research we do, but these are our ideas. We develop the concepts, write the protocols, seek funding, and hope to change the lives of children throughout the world.” — CHOC Infectious Diseases Medical Director Antonio Arrieta, M.D.

CHOC Infectious Diseases also participates in several collaborative pharmacokinetic (PK) trials to reassess the efficacy, safety and dosing of new antimicrobial agents. Many of these trials are industry-sponsored and focus on neonatal, oncology and cystic fibrosis patients. CHOC Infectious Diseases is also collaborating with Duke University in a Eunice Kennedy Shriver National Institute of Child Health and Human Development-funded grant to conduct PK trials for neonates, and with the University of California, Los Angeles on a NIH grant for pediatric HIV.

Training Tomorrow’s “Clinician Scientists”

During his medical training, Dr. Arrieta was taught to “always stay curious and answer questions with research.” He passes that philosophy on to CHOC residents by encouraging them to also participate in research and submit their results. As a bonus, the resident gets to present any accepted poster or paper. In recent years, CHOC residents have presented at meetings in Australia, Switzerland and France.

“We believe emphatically in training scientific doctors because answering questions through research is integral to being a clinician,” Dr. Arrieta said. “Without that, they will not be complete. Many CHOC residents have gone on to become scientists and teachers, and that makes us very proud of what we do.”


Preliminary Pneumococcal Vaccine Data Soon Available

CHOC Infectious Diseases is assessing the impact of a new vaccine in reducing invasive pneumococcal disease and pneumonia. Similar to previous work conducted after the introduction of the first pneumococcal conjugate vaccine, and published in the Journal of Pediatric Infectious Diseases in 2011, CHOC is conducting an annual three-year interim analysis and then a final five-year study. Initial results will be available soon to share with parents about the importance of immunization. To learn more about Research at CHOC, please visit www.choc.org/research.