Study Led by Cincinnati Children's Finds Gene Expression Pattern That Could Provide Path to Improved Diagnosis and Treatment of Pediatric Septic Shock

Thursday, July 26, 2007

CINCINNATI -- A consortium of researchers headed by Cincinnati Children's Hospital Medical Center has discovered a gene expression pattern that could lead to improved diagnosis and treatment of pediatric septic shock -- still a serious public health problem despite today's potent antibiotics and pediatric intensive care units.

Consistent with Cincinnati Children's increased emphasis on personalized and predictive medicine -- where diagnosis and treatment coincide with a person's genetic predisposition -- the study involves the largest gene expression analysis to date of blood samples from children with septic shock. It found new evidence linking adverse clinical outcomes with the decreased expression of genes that encode proteins involved in zinc regulation. This unexpected finding suggests these proteins and zinc regulation could provide a target for therapeutic intervention to inhibit septic shock's progression to multiple organ failure.

"Zinc was not even on our radar screen for this disease process," said Hector Wong, MD, professor of Pediatrics and director of Critical Care Medicine at Cincinnati Children's. "This study demonstrates the potential power of genomic medicine for discovery and the generation of novel hypotheses. We are ultimately interested in determining whether or not there are biologically significant gene expression profiles that distinguish survivors from non-survivors. The rationale is to discover novel biomarkers of poor outcome and novel therapeutic targets as means for developing more effective treatment strategies."

The study -- published in the July issue of Physiological Genomics -- and consortium were led by Dr. Wong. The paper describes how comparative gene expression analysis of blood samples from children identified 63 genes expressed differently in patients with septic shock. This includes two forms of metallothionein where higher levels of metallothionein and lower levels of zinc were associated with increased chance of death. A total of 57 children participated in the study, which used individual micro-array chips to analyze samples from 15 control patients without septic shock and 42 patients with septic shock, including nine fatal cases.

The consortium was composed of 10 medical centers:

• Cincinnati Children's Hospital Medical Center
• Mott Children's Hospital at the University of Michigan
• Children's Hospital and Research Center Oakland, Oakland, CA
• Children's Hospital of Philadelphia
• Children's Mercy Hospital, Kansas City
• Penn State Children's Hospital, Hershey, PA
• University of Virginia Medical Center, Charlottesville, VA
• Newark Beth Israel Medical Center, Newark, NJ
• The University of Alabama at Birmingham and DuPont Hospital for Children, Wilmington, DE

Researchers at Cincinnati Children's continue to investigate the potential for analyzing zinc levels as way to understand the biology of septic shock and allow for more effective therapeutic intervention. This includes the possibility of using zinc supplementation as a form of treatment.

Cincinnati Children's Hospital Medical Center, one of the leading pediatric research institutions in the nation, is dedicated to changing the outcome for children throughout the world. Cincinnati Children's ranks second among all pediatric institutions in the United States in grants from the National Institutes of Health. It has an established tradition of research excellence, with discoveries including the Sabin oral polio vaccine, the surfactant preparation that saves the lives of thousands of premature infants each year, and a rotavirus vaccine that saves the lives of hundreds of thousands of infants around the world each year. Current strategic directions include the translation of basic laboratory research into the development of novel therapeutics for the treatment of disease, and furthering the development of personalized and predictive medicine.