Federal grant supports advances in infant heart disease at Children's Hospital of Philadelphia


Goal: Speed movement of genetic research to bedside treatments

Under a new federal initiative to foster "bench to bedside" studies, The Children's Hospital of Philadelphia has received a five-year grant from the National Heart, Lung and Blood Institute (NHLBI) for a coordinated research program in the causes and treatments of heart disease in children. Children's Hospital will receive $3.8 million in the first year of the grant, with the Hospital's five-year total estimated at more than $19 million.

Children's Hospital is one of four centers nationwide that the NHLBI has designated a Specialized Center of Clinically Oriented Research (SCCOR) in Pediatric Heart Development and Disease. The Institute's SCCOR program is a new initiative designed to speed the process by which advances in basic scientific knowledge are translated into innovative treatments for patients.

Pediatric cardiologist Robert J. Levy, M.D., is the principal investigator of the SCCOR program at Children's Hospital, entitled, "Genetic Mechanisms in Pediatric Heart Disease." The SCCOR award builds on an existing, very robust pediatric cardiology program at the hospital. The Cardiac Center at Children's Hospital is among the nation's largest and most comprehensive clinical programs in pediatric cardiology, cardiac surgery and cardiac anesthesia. The Cardiac Center's research program has become a major focal point both nationally and internationally for investigating the genetic basis of congenital heart disease.

"Over the past decade, investigators at Children's Hospital have made a series of discoveries supporting the hypothesis that congenital heart abnormalities are caused by gene defects," said Dr. Levy. "The new SCCOR grant will seek to transform our fundamental hypothesis into a translational approach that yields practical treatments."

Congenital heart abnormalities, which occur in approximately one in 100 live births, are the largest contributor to deaths from birth defects. Although advances in medical and surgical treatments have greatly improved survival for newborns and children with heart defects, many survivors face challenges in overall health and longer-term outcomes. Moreover, for many heart defects, the underlying cause remains unknown.

Drawing on the talents of multidisciplinary teams is an important feature of the SCCOR program. At The Children's Hospital of Philadelphia, the program relies on longstanding collaborations among cardiologists, cardiac surgeons and geneticists. "We are aiming to ultimately develop new tools such as gene-based diagnoses of congenital heart disease, gene therapy for congenital heart disease, and improved biologically-based materials for heart surgery, such as heart valves," said Dr. Levy.

The SCCOR program at Children's Hospital will encompass five projects, all designed to advance previous investigations by the researchers involved. Project 1, headed by Dr. Levy, will study cellular and molecular mechanisms influencing the usability of replacement heart valves for children with heart disease. Project 2, led by Deborah Driscoll, M.D., of the Division of Human Genetics and Molecular Biology, will analyze the role of specific genes involved in early cardiac development in children with defects of the outflow tract, the vessels and valves by which blood is pumped out of the heart.

Project 3, headed by pediatric cardiologist Elizabeth Goldmuntz, M.D., will study how genetic alterations affect heart anatomy and clinical outcomes in children with complex congenital heart disease. Project 4, led by Ian Krantz, M.D., a clinical geneticist, will study the associations between heart defects and gene rearrangements in and near the telomeres regions of human chromosomes that have been seldom studied until recently.

The fifth SCCOR project is led by Beverly Emanuel, Ph.D., Co-Director of the SCCOR program at Children's Hospital, and director of the Division of Human Genetics and Molecular Biology. Dr. Emanuel led pioneering research on the links between deletions of genetic material on human chromosome 22 and congenital heart disease. Project 5 will draw on data from the Human Genome Project to identify genes critical to early heart development, specifically those associated with chromosomal breakpoints. Those breakpoints are vulnerable regions at which chromosomes may break apart and rearrange themselves. As with all five projects, the long-term goal is to seek research directions that can lead to clinical benefits for patients and families.

Core facilities for clinical subject recruitment, cell culture and DNA analysis, gene expression and histology, and bioinformatics and data analysis will provide vital support to the individual projects.

In addition to The Children's Hospital of Philadelphia, the other centers included in the NHLBI's five-year, $68 million SCCOR program award are Boston Children's Hospital, the University of Pittsburgh and Children's Hospital of Pittsburgh, and Cincinnati Children's Medical Center. "These centers address a critical public health need for research that examines the basis of congenital and acquired heart disease in children," said Acting NHLBI director Barbara Alving, M.D., in announcing the SCCOR awards.

The Cardiac Center at The Children's Hospital of Philadelphia is a comprehensive center for the care of infants, children and young adults with congenital and acquired heart disease. It was recently ranked as the best pediatric cardiac program in the United States by Child magazine.

Source: Eurekalert & others

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