Bench to Bedside

May 2013

CHOP Awarded $3.1 Million Grant to Fund Behavioral Interventions Study


A failure to address the emotional and behavioral problems of school-age children can have serious, life-changing ramifications, including poor grades, suspension and expulsion, and problems with the law later in life. However, studies show that only 1 in 5 children with emotional and behavioral disorders receive mental health services, with low-income and ethnically diverse children lagging far behind their middle class, Caucasian counterparts.

At the heart of this disparity is a shortage of specialized services in low-income communities, the high cost of these services, and the stigma attached to using such services. Minority students in urban school districts are especially at risk due to the anxiety and deleterious effects of living in unsafe and deprived neighborhoods.

Moreover, evidence-based interventions are not successfully deployed in urban schools. Such interventions are all too often derailed by inadequate training and poor implementation by service providers in the school, and a lack of resources to consult outside behavioral health providers.

The National Institute of Child Health and Human Development recently awarded Children’s Hospital a $3.1 million grant to study the level of support school personnel needed to effectively implement an intervention program called School-Wide Positive Behavioral Interventions and Supports (SW-PBIS) for typically developing students as well as students with, or at risk for, externalizing or anxiety disorders.

SW-PBIS is a comprehensive service delivery strategy that, by combining universal and targeted interventions to address students’ emotional and behavioral issues, can help improve overall school climate, perceived school safety, and student academic performance. The program focuses on preventing new cases of problem behaviors through school-wide discipline, classroom behavior management, and effective instructional practices.

The CHOP study, which will be led by Ricardo Eiraldi, PhD, will examine whether school personnel can implement the components of a two-tier SW-PBIS program with the same level of fidelity, integrity and effectiveness when they receive a relatively low level of support from coaches and supervisors as they can with a high level of support. Dr. Eiraldi and his team partnered with the School District of Philadelphia to select six schools in North Philadelphia for participation in the project.

The schools will be randomly assigned to receive either a high level or a low level of training and consultation to implement SW-PBIS interventions over a five-year period. The investigators will additionally study the impact of high and low levels of support on students’ mental health disparities and academic productivity, as well as the cost-effectiveness of the respective support levels.

“We know that school personnel can implement SW-PBIS with fidelity from a program development grant project we already conducted in two other schools located in the same area of the school,” Dr. Eiraldi said. “Now we would like to know how much support school personnel actually need in order to implement the program with fidelity and effectiveness.”

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CHOP Cardiologist Helps Discover a Cause for Abnormal Heart Vessels


A pediatric cardiologist at The Children’s Hospital of Philadelphia is a first author of new research identifying a mutation that disrupts the formation of veins bringing blood to the heart very early in development. The abnormal connections and blood flow result in so-called “blue babies” — newborns with a potentially deadly heart condition.

Karl Degenhardt, MD, PhD, of the Cardiac Center at Children’s Hospital, is one of three co-first authors of a study published recently in Nature Medicine. The study leader and senior author is Jonathan A. Epstein, MD, chair of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania.

The researchers analyzed the congenital condition called total anomalous pulmonary venous connection (TAPVC), in which pulmonary veins fail to connect normally to the heart’s left atrium. Because these veins carry oxygen-rich blood from the lungs, this faulty connection means that blood circulating to the body carries insufficient oxygen — hence the blue skin color in newborns with this condition.

Working in animal models, the study team focused on a mouse gene that produces a key signaling protein called Sema3d. When a mutation disrupts normal biological signals, blood vessels form in the wrong location and the circulation goes seriously astray. The researchers then analyzed DNA from 40 CHOP patients with this TAPVC and a related milder condition, and found a mutation in the human gene that corresponds to those studied in mice.

“Although further studies need to be done, this research shows a new mechanism for how a particular gene mutation may cause this important congenital heart condition in children,” said Dr. Degenhardt. While the study does not immediately affect treatment, it may provide a starting point for future therapies targeting the specific gene or signaling pathway.

The authors also point out that further research on the same signaling genes and proteins may suggest treatments for other diseases involving blood circulation, including cancers, retinal disorders and vascular conditions.

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Study Identifies BMI-Associated Loci in Individuals of African Descent


The United States has a weight problem: according to the CDC, more than one-third of American adults are obese. Moreover, as of 2010 one-third of children were either overweight or obese, with the rates of obesity doubling in children and tripling in adolescents in the past thirty years. And some groups are more inclined to be obese than others, with non-hispanic blacks 51 percent more likely than whites to be obese, for example.

A recently published study may help researchers better understand why some populations are more susceptible to obesity than others. Struan Grant, PhD, associate director of The Children’s Hospital of Philadelphia’s Center for Applied Genomics (CAG), co-authored a study that discovered new loci associated with body mass index (BMI) in adults of African ancestry.

Previous genome-wide association studies had identified 36 BMI-associated loci. While those studies mainly investigated individuals of European descent, in the current study the researchers conducted a meta-analysis to determine whether more than 3.2 million single nucleotide polymorphisms were associated with BMI in men and women of African ancestry. In all, more than 70,000 men and women of African descent were studied.

In addition to Dr. Grant, Children’s Hospital’s Hakon Hakonarson, MD, PhD, director of CAG, Brendan Keating, PhD, CAG lead clinical data analyst and Faculty member in UPenn Pediatrics and Surgery, and CAG bioinformatics specialist Jonathan Bradfield, also contributed and co-authored the study. More than 200 researchers representing over 50 institutions, including the Broad Institute, the National Human Genome Research Institute, and Johns Hopkins University, took part in the investigation. The study was published online recently in Nature Genetics.

The research group discovered two new loci — 5q33 and 7p15 — associated with BMI in people of African ancestry, while a third, 6q16, was found to be suggestive of an association. “These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations,” the researchers say.

“Our sizeable genetic database of African American children played a crucial role in this study, lending further support to the loci initially detected in the adult cohorts” Dr. Grant added.

Children’s Hospital researchers have been associated with a number of previous investigations related to the current study, including one that identified genes associated with childhood obesity.

Last year CHOP investigators, as part of the Early Growth Genetics Consortium, helped identify two new gene variants that increase the risk of childhood obesity. After performing a meta-analysis of 14 previous studies, the study’s authors identified two novel loci and the suggestion of an association for two other gene variants, none of which had previously been implicated in obesity. CAG’s Struan Grant was the senior author of the study while Jonathan Bradfield acted as co-first author, which was published in Nature Genetics.

The current study’s findings, meanwhile, “demonstrate the importance of conducting genetic studies in diverse populations to identify new susceptibility loci for common traits,” the investigators note.

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Muscular Dystrophy Association Grant Could Lead to New Treatment


A new grant award will allow an investigator from The Children’s Hospital of Philadelphia to study the effectiveness of certain drugs called retinoid agonists in slowing or preventing muscle degeneration in individuals with muscular dystrophy. Findings from the study could lead to a new, ground-breaking treatment for those individuals.

Muscular dystrophy is a group of genetic disorders that causes progressive loss of muscle structure and muscle contractility, strength, and function. The disease is characterized by chronic inflammation, muscle cell death, the decrease and eventual exhaustion of satellite cells, and increase and infiltration of fat and fibrous tissue. Current treatment options are limited to symptom management.

With a $405,000, three-year grant from the Muscular Dystrophy Association (MDA), Masahiro Iwamoto, PhD, DDS, a research scientist of the Translational Research Program in Pediatric Orthopaedics at Children’s Hospital and research associate professor of Orthopedics at the University of Pennsylvania School of Medicine, will test his hypothesis that a retinoic acid receptor-gamma (RARg) agonist, a synthetic retinoid which selectively activates RARg could be used to slow and even stop the disease progression of muscular dystrophy.

Retinoic acid, an active form of vitamin A, plays an important role in the functioning of numerous organs, including musculoskeletal systems. However, the clinical use of natural retinoids is limited to the treatment of certain malignant tumors and skin conditions due to side effects caused by the simultaneous activation of multiple retinoid receptors. To improve drug effectiveness and reduce side effects, synthetic receptor-specific retinoid agonists have been developed.

Dr. Iwamoto and his team recently discovered that a class of selective RARg agonist block the formation of bone within muscle and prevents muscle degeneration. The findings were part of his research into heterotopic ossification (HO), the pathological formation of ectopic bone within soft tissue, primarily skeletal muscles.

More than 10 percent of patients undergoing invasive surgeries can develop a form of HO and 65 percent of seriously wounded soldiers also develop the disease, which causes chronic pain, limited motion and other complications.

With the MDA grant, Dr. Iwamoto will build on his HO research to learn more about RARg properties and how the molecule contributes to the repair and maintenance of skeletal muscle.  An RARg agonist known as R667 has already shown some promise in the lab and has been tested in humans for other conditions. Dr. Iwamoto will test whether R667 has the potential for treating muscular dystrophy in mice without serious side effects.

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Drexel Undergrad, CHOP Advisor Present Brain Research on Capitol Hill


A Drexel University undergraduate, accompanied by her CHOP faculty advisor, recently had the opportunity to present her traumatic brain injury research to a group of elected officials in Washington, D.C. at Posters on the Hill. Organized by the Council on Undergraduate Research (CUR), this annual event gives undergraduate investigators the chance to share their work directly with members of Congress, and is “an important opportunity for lawmakers to see how federal dollars make a real difference for students and faculty and nurture interest in research and postsecondary study.”

Matthew R. Maltese, PhD, director of Biomechanics Research in Children’s Hospital’s Department of Anesthesiology and Critical Care Medicine, acted as Drexel University undergraduate Veronika Legkobitova’s faculty advisor. Legkobitova, a mechanical engineering student at Drexel, was one of 60 undergraduates from across the country to be chosen from more than 800 applicants to attend Posters on the Hill.

Dr. Maltese was teamed up with Legkobitova through Drexel’s STAR Scholars program, which pairs “high-achieving” undergraduates with faculty mentors so students can “explore a major course of study, and gain practical skills and valuable research experience for their future career or course of graduate study.”

While at Posters on the Hill, Legkobitova presented her research, “Effect of Brain Stem Displacement on Traumatic Brain Injury.” Her project was focused on improving finite element models — a type of computer model used to predict injury — by measuring the boundary condition of the foramen magnum (which transmits the medulla oblongata and spinal nerves) during head movement.

She and Dr. Maltese also had the chance to meet with several officials and staff members, including Philadelphia’s own Rep. Chaka Fattah, as well as staffers from the offices of Sen. Pat Toomey and Rep. Patrick Meehan.

Legkobitova also presented Rep. Fattah with the 2013 Honorary CUR Fellowship Award, which is given annually “to leaders working to promote undergraduate research and the mission of the CUR.” Since 1995 Congressman Fattah has represented Pennsylvania’s 2nd District, and is the senior Democrat on the House Appropriation Committee’s Subcommittee on Commerce, Justice, Science, and Related Agencies.

“It was really interesting to see a different part of research: the law-making part,” Legkobitova said. “Meeting the actual people involved in deciding what government funding goes into grants and learning their personal opinions on it was eye-opening. I didn’t realize how many people were invested in the research that even undergraduates do, and how important that research can be to students, professionals, and society.”

For more information about Posters on the Hill, see the Council on Undergraduate Research’s page. To learn more about the STAR scholars program, see Drexel University’s page.

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New Study Offers Biliary Atresia Clues


A new genetic study by The Children’s Hospital of Philadelphia researchers may shed light on the causes of the rare childhood disease biliary atresia. The leading cause of liver transplantation in children, biliary atresia (BA) is a rare, life-threatening condition in which the ducts that carry bile from the liver to the gallbladder become blocked.

Children’s Hospital’s Randy Matthews, MD, PhD, led this new collaborative genetic study of BA, a condition occurring exclusively in neonatal livers. A relatively rare disease, BA affects approximately one out of every 15,000 infants, and is more common in Asians and African Americans. If left untreated, BA can lead to liver damage and cirrhosis of the liver, and patients with BA often require liver transplants.

With this study, Dr. Matthews and other CHOP researchers, including Marcella Devoto, PhD, and Nancy B. Spinner, PhD, hoped to better understand BA’s etiology, which, while still poorly understood, is “believed to involve exposure of a genetically susceptible individual to certain environmental factors.” Both Drs. Matthews and Spinner are members of Children’s Hospital’s Fred and Suzanne Biesecker Pediatric Liver Center.

The study — which was funded in part by the Center, as well as the NIH and the Childhood Liver Disease Research and Education Network, a network of clinicians and researchers working “to improve the lives of children and families dealing with rare liver diseases” — was published recently in Gastroenterology.

“Despite recent inroads into the understanding the mechanisms leading to fibroinflammatory damage to the biliary tree, uncovering the cause of BA continues to be a major challenge,” Dr. Matthews noted. Because BA is so rare, and because there have been few documented cases showing clear familial inheritance, studies into the condition’s possible genetic causes have been difficult, Dr. Matthews said.

After searching for copy number variations (CNVs) — losses or gains in DNA sequence — in patients with BA compared to healthy individuals, Dr. Spinner and her team identified a candidate gene, GPC1. Moving to an animal model, Dr. Matthews and his team then studied the effects of using morpholino antisense oligonucleotides to reduce expression of gpc1 in zebrafish.

Zebrafish, a type of tropical freshwater fish that is commonly used in a variety of scientific and medical studies, “offer a facile animal model for this type of ‘precision medicine’, as they are more amenable to rapid genetic manipulation than mice, and can be analyzed more quickly as well due to their rapid and ex utero development,” Dr. Matthews pointed out.

The researchers showed that disruption of gpc1 (as the gene is known in zebrafish) led to biliary defects in zebrafish. This finding, combined with the fact that the investigators also found “GPC1 abnormalities in all BA patient liver samples examined,” support “a potential role for GPC1 as a susceptibility gene for BA,” Dr. Matthews said.

“This is the first study to identify a potential BA risk gene in patients and demonstrate functional defects in the biliary system in model organism studies,” the study’s authors note.

This study builds on previous work by Dr. Spinner’s lab, which associated a region of chromosome 2 with BA. Studies of other possible BA-associated genes are currently underway in the Spinner lab, and Dr. Matthews noted that any future investigations into BA’s causes — and possible treatments — would make use of that work.

While “the ability to test infants for genetic susceptibility to BA is clearly far off,” future studies that shed light on biliary atresia’s pathogenesis could help “identify treatments that are more effective than the existing therapy,” Dr. Matthews said. That said, once tests for BA genetic susceptibility are developed, they will likely include testing for GPC1 defects, he added.

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CHOP Scientist Contributes to Heart Defect Study


A physician-scientist from The Children’s Hospital of Philadelphia, Elizabeth Goldmuntz, MD, is one of the senior leaders of a research consortium reporting important gene changes that may help explain why children are born with heart defects.

CHOP is one of five centers in the Pediatric Cardiac Genetics Consortium, supported by the National Heart, Lung and Blood Institute, part of the National Institutes of Health. The Consortium published its first major study findings recently in Nature.

The current study identified de novo mutations predicted alter proteins in genes expressed in the developing heart. The mutations were particularly abundant in histone-modifying genes, which play key roles in early human development by affecting whether other genes become active.  De novo mutations are changes in the gene sequence that are not present in the parents but found only in the affected child as a new alteration. Because these mutations were predicted to change protein function, they are likely to be harmful.

The researchers compared 362 families in which a child had a severe heart defect to 264 control families, analyzing their exomes — the protein-coding sections of DNA — to determine which mutations were more common in severe cases.

“Collectively, these results suggest that protein-altering, de novo point mutations occur in hundreds of genes, and may account for about 10 percent of severe congenital heart disease,” said Dr. Goldmuntz, the consortium’s principal investigator at CHOP and a pediatric cardiologist at CHOP’s Cardiac Center.

“Congenital heart disease itself is the most frequent serious birth defect, so as we go on to discover more of these gene alterations during early heart development, we will be better able to provide genetic counseling and refine patient care for many families and children,” she added.

In addition to CHOP, the other four centers in the Pediatric Cardiac Genetics Consortium are Yale University, Columbia University, Mt. Sinai School of Medicine, and Harvard University.

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Children’s Hospital Autism Expert Consulted for Placenta Study Coverage


Tara Wenger, MD, PhD, a Pediatric Genetics fellow in the Center for Autism Research, was recently featured in a number of articles about an exciting new study of autism. The study examined whether trophoblast inclusions — microscopic, abnormal folds in the tissue of the placenta — could serve as a predictor of autism in children from families at high risk for autism spectrum disorder (ASD).

The study, which was led by the Yale School of Medicine’s Harvey J. Kliman, MD, PhD, was published recently in Biological Psychiatry.

The researchers discovered that “the placentas from women whose fetuses are at elevated risk for autism are markedly different from control placentas.” This finding “has the possibility of identifying newborns at risk for ASD who might benefit from targeted early interventions aimed at preventing or ameliorating behavioral symptoms and optimizing developmental outcomes,” the researchers write.

“It would be really exciting to have a real biomarker and especially one that you can get at birth,” Dr. Wenger told the New York Times for their article on the study.

After receiving her MD/PhD from the University of Rochester School of Medicine and Dentistry, Dr. Wenger joined Children’s Hospital in 2008 for a residency in Pediatrics and Medical Genetics.

She first became interested in ASD as an undergraduate, while working at clinic for children with autism. In graduate school she studied children with ASD who had been exposed to valproic acid — an anticonvulsant used often used to treat epilepsy — in utero.

Dr. Wenger’s current research is focused on identifying the underpinnings of ASD in environmental and genetic exposure syndromes. “By understanding the mechanisms for development of ASD in these well-defined cohorts, we hope to identify pathways that may be important in the development of idiopathic ASD and could be amenable to pharmacologic treatment,” Dr. Wenger has said.

The Biological Psychiatry study “provides additional evidence that many cases of autism are really starting to develop well before a child is born,” Dr. Wenger said in another article on WBUR Boston’s CommonHealth blog.

“A lot of people think of autism as something that happens after you’re born — because in toddlerhood is when you start to see the signs,” she noted. “But as you look at the brains, it really suggests that most of these cases are originating very early in pregnancy.”

To learn more about the exciting autism research being conducted at The Children’s Hospital of Philadelphia, see the Center for Autism Research.

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Converting Stem Cells to Brain Cells Sheds Light on Neural Development


Stem cells have the unique ability to develop, or differentiate, into other kinds of cells in the body. Researchers have now manipulated human stem cells so that they produce the types of brain cells that play important roles in neurodevelopmental disorders such as epilepsy, schizophrenia, and autism.

This new model cell system will allow neuroscientists to investigate normal brain development, as well as to identify specific disruptions in biological signals that may contribute to neuropsychiatric diseases.

The research, conducted by scientists from The Children’s Hospital of Philadelphia and Memorial Sloan-Kettering Cancer Center, harnesses human embryonic stem cells, which differentiate into a broad range of different cell types. The investigators directed the stem cells into becoming cortical interneurons — a class of brain cells that, by releasing the neurotransmitter GABA, controls electrical firing in brain circuits.

“Interneurons act like an orchestra conductor, directing other excitatory brain cells to fire in synchrony,” said study co-leader Stewart A. Anderson, MD, a research psychiatrist at Children’s Hospital. “However, when interneurons malfunction, the synchrony is disrupted, and seizures or mental disorders can result.”

Dr. Anderson and his study co-leader Lorenz Studer, MD, of the Center for Stem Cell Biology at Sloan-Kettering, derived interneurons in a laboratory model that simulates how neurons normally develop in the human forebrain. “Unlike, say, liver diseases, in which researchers can biopsy a section of a patient’s liver, neuroscientists cannot biopsy a living patient’s brain tissue,” said Dr. Anderson.

It is therefore important to produce a cell culture model of brain tissue for studying neurological diseases, he added. Significantly, the human-derived cells in the current study also “wire up” in circuits with other types of brain cells taken from mice, when cultured together. Those interactions, Dr. Anderson said, allowed the study team to observe cell-to-cell signaling that occurs during forebrain development.

Dr. Anderson and his colleagues are using their cell model to better define molecular events that occur during brain development. By selectively manipulating genes in the interneurons, they hope to better understand how gene abnormalities may disrupt brain circuitry and give rise to particular diseases.

Those studies could ultimately help inform drug development by identifying molecules that could offer therapeutic targets for more effective treatments of neuropsychiatric diseases.

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Cancer Expert Honored with Pediatric Oncology Award and Lecture


A pediatric oncologist with the Cancer Center at The Children’s Hospital of Philadelphia recently received a national award highlighting his lifetime research on neuroblastoma, the most common solid tumor of childhood. The American Society of Clinical Oncology conferred one of its highest awards on Garrett M. Brodeur, MD, who received the Pediatric Oncology Award and delivered the Pediatric Oncology Lecture.

The Award and Lecture, held during the ASCO annual meeting in Chicago, recognizes “outstanding scientific work of major importance to the field of pediatric oncology” during the course of a career. Dr. Brodeur is an expert in neuroblastoma.

A cancer of the peripheral nervous system that typically appears as a tumor in a child’s abdomen or chest, neuroblastoma varies greatly in severity, ranging from forms that spontaneously disappear to high-risk subtypes that are difficult to cure. Because of this variability, researchers have sought ways to predict the course of disease in order to select the most appropriate treatment for each patient. The underlying assumption of this approach is that better understanding of the biology of this cancer will allow pediatric oncologists to avoid undertreating or overtreating a child.

Over his career, Dr. Brodeur has focused on identifying the genes, proteins and biological pathways that give rise to neuroblastoma and drive its clinical behavior. He also has built on this knowledge to develop more effective and less toxic treatments for children by targeting specific pathways.

His research first demonstrated in the 1980s that when neuroblastoma cells developed multiple copies of the MYCN gene, a process called amplification, a high-risk subtype of neuroblastoma occurs, necessitating more aggressive treatment. This discovery ushered in the current era of genomic analysis of tumors, both in adult and pediatric oncology. Profiling specific molecular alterations in a given patient’s tumor helps oncologists to predict that patient’s outcome and select the most appropriate treatment.

Dr. Brodeur and his colleagues also identified deletions of important genes on chromosome 1 and on chromosome 11 as markers of high-risk neuroblastoma. He has collaborated with other CHOP researchers who identified the ALK gene as the gene responsible for most cases of hereditary neuroblastoma.

Another major focus of his research has concerned receptor tyrosine kinases, a family of signaling proteins that control the clinical behavior of neuroblastomas. His preclinical work led to a clinical trial with a novel drug that selectively blocks TRK signaling. He is now working on second-generation TRK inhibitors, as well as on nanoparticle delivery systems to treat patients more effectively, and with less toxicity.

Dr. Brodeur has been a member of the CHOP medical staff since 1993 and holds the Audrey E. Evans Endowed Chair in Pediatric Oncology at the Hospital. He also is a professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania, where he is an associate director of the Abramson Cancer Center. Before arriving at CHOP, Brodeur did his fellowship in Pediatric Hematology-Oncology at St. Jude’s Children’s Research Center and a postdoctoral fellowship in Molecular Genetics at Washington University School of Medicine in St. Louis, where he remained until coming to CHOP.

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CHOP, Penn Gene Therapy Trial for Blindness Honored


A groundbreaking clinical trial of gene therapy for a form of congenital blindness, sponsored by The Children’s Hospital of Philadelphia in collaboration with Penn Medicine, was recently recognized with the Distinguished Clinical Research Achievement Award from the Clinical Research Forum, an organization of clinical research centers, industry, and volunteer groups.

Based in Washington, D.C., the Clinical Research Forum (CRF) provides “leadership to the national clinical and translational research enterprise,” and promotes “understanding and support for clinical research and its impact on health.”

That recent award given to CHOP and Penn is the second highest in the CRF’s annual Top 10 Clinical Research Achievement Awards. Recognizing studies published in 2012, the CRF focused on a Feb. 2012 article in Science Translational Medicine, co-authored by researchers from CHOP and the Perelman School of Medicine at the University of Pennsylvania. The authors reported on the most recent phase of a clinical trial for Leber’s congenital amaurosis (LCA), a rare retinal disease that progresses to total blindness by adulthood.

The study team reported on further improvements in vision in three adult patients previously treated in one eye who then received the same innovative gene therapy in the second eye.

This LCA research is an ongoing collaboration among Jean Bennett, MD, PhD, F.M. Kirby professor of Ophthalmology at the University of Pennsylvania School of Medicine, CHOP’S Katherine A. High, MD, director of the Center for Cellular and Molecular Therapeutics (CCMT), and Albert M. Maguire, MD, of Penn Medicine and CHOP.

Dr. High, a pioneering gene therapy researcher, directs the CCMT, which is sponsoring the clinical trial in LCA, and which manufactured the genetically engineered virus used to carry the therapeutic gene. Dr. Maguire, a retina specialist, injected the corrective gene into the eyes of adult and pediatric study subjects at Children’s Hospital.

As widely reported in October 2009, this clinical trial of gene therapy achieved dramatic results in children with LCA. Building on their previous work, the research team is now conducting the first Phase 3 gene therapy study for genetic disease in the U. S. This is also the world’s first Phase 3 gene therapy study for a non-lethal disorder. If successful, it could lead to the first approved gene therapy product in the United States.

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Requesting Applications for the 2014 Pew Scholars Program in Biomedical Sciences


We are pleased to solicit internal applications to be considered for the 2014 Pew Scholars Program in Biomedical Sciences. The Pew Scholars Program provides funding to young investigators of outstanding promise in science relevant to the advancement of human health. The candidates are individuals who are in their first few years of their appointment at the assistant professor level. The award provides $240,000 in flexible support — $60,000 per year for a four-year period.

Candidates interested in applying should contact Phyliss Quail at 215-590-1418 or for the internal application guidelines. All candidates will need to include a Letter of Support from the chair of their division to include as part of the internal application package.

Internal Deadline — 5:00 p.m. Friday, June 21, 2013


*Applicants with committed awards that overlap for the first two years of the Pew Scholars Program from the Searle Scholars Program, Rita Allen Foundations Scholars, Burroughs Wellcome Fund Career Award for Medical Scientists, Beckman Young Investigator Program, Ellison New Scholar Award, W.M. Keck Foundation, Damon Runyon-Rachleff Innovation Award, and the Kimmel Scholar Award are not eligible.

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