New network will advance treatments for children


Three leaders from Children’s National Health System are among the investigators of a new FDA-funded program created to launch a global clinical trials network. The initial $1 million grant from the Food and Drug Administration (FDA) establishes a network among the Institute for Advanced Clinical Trials for Children (I-ACT for Children), the National Capital Consortium for Pediatric Device Innovation (NCC-PDI) (affiliated with Children’s National), PEDSnet, the James M. Anderson Center for Health Systems Excellence and the Critical Path Institute, to address the unmet medical needs of children by improving quality and efficiency in developing innovative pediatric drugs and devices.

Along with the fiscal 2017 funds, there is a potential for $1 million in funding each year for an additional four years to I-ACT for Children, contingent on annual appropriations and the availability of funding. I-ACT for Children is a new independent, nonprofit organization that works to improve the planning and completion of pediatric clinical trials. PEDSnet and the Anderson Center will serve as the network’s data and learning core, while the Critical Path Institute will serve as the regulatory science core and NCC-PDI will serve as the medical device core.

From Children’s National, the investigators include: Peter Kim, M.D., Ph.D., vice president of the Sheikh Zayed Institute for Pediatric Surgical Innovation; Kolaleh Eskandanian, Ph.D., executive director of the Sheikh Zayed Institute and NCC-PDI and Johannes van den Anker, M.D., Ph.D., division chief of Clinical Pharmacology and vice chair of Experimental Therapeutics.

“We are pleased that this grant addresses innovative reengineering of the pediatric device trials system,” says Eskandanian. “In contrast with drug trials, device trials are generally less optimally understood in academic medical centers and clinical sites.”

She explains that children have medical device needs that are considerably different from adults. Designing devices for children requires considerations such as growth and development, anatomical and physiological differences. Often, the lack of available devices for children forces clinicians to use an adult device off-label or to improvise. Off-label use may be the only option, but such use can bring risks of serious adverse events that could be avoided if there were more FDA–approved pediatric devices.

“Thanks to partnership with I-ACT we will be able to address the pressing need to improve clinical trials and post-market monitoring of pediatric devices,” says Eskandanian.

Leading the network as principal investigator is Edward Connor, M.D., president of I-ACT for Children and an emeritus professor of Pediatrics, Microbiology, Immunology, and Tropical Medicine at George Washington University School of Medicine and Children’s National.

Work has been initiated to integrate network components and engage public and private shareholders. Next steps include selecting priority projects for implementation in 2018 and beyond, and scaling the network in North America and abroad.

Funding for this work was made possible, in part, by the Food and Drug Administration through grant 1 U18 FD 006297. Views expressed in written materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

Nobuyuki Ishibashi

Children’s receives NIH grant to study use of stem cells in healing CHD brain damage

Nobuyuki Ishibashi

“Bone marrow stem cells are used widely for stroke patients, for heart attack patients and for those with developmental diseases,” explains Nobuyuki Ishibashi, M.D. “But they’ve never been used to treat the brains of infants with congenital heart disease. That’s why we are trying to understand how well this system might work for our patient population.”

The National Institutes of Health (NIH) awarded researchers at Children’s National Health System $2.6 million to expand their studies into whether human stem cells could someday treat and even reverse neurological damage in infants born with congenital heart disease (CHD).

Researchers estimate that 1.3 million infants are born each year with CHD, making it the most common major birth defect. Over the past 30 years, advances in medical technology and surgical practices have dramatically decreased the percentage of infants who die from CHD – from a staggering rate of nearly 100 percent just a few decades ago to the current mortality rate of less than 10 percent.

The increased survival rate comes with new challenges: Children with complex CHD are increasingly diagnosed with significant neurodevelopmental delay or impairment. Clinical studies demonstrate that CHD can reduce oxygen delivery to the brain, a condition known as hypoxia, which can severely impair brain development in fetuses and newborns whose brains are developing rapidly.

Nobuyuki Ishibashi, M.D., the study’s lead investigator with the Center for Neuroscience Research and director of the Cardiac Surgery Research Laboratory at Children’s National, proposes transfusing human stem cells in experimental models through the cardio-pulmonary bypass machine used during cardiac surgery.

“These cells can then identify the injury sites,” says Dr. Ishibashi. “Once these cells arrive at the injury site, they communicate with endogenous tissues, taking on the abilities of the damaged neurons or glia cells they are replacing.”

“Bone marrow stem cells are used widely for stroke patients, for heart attack patients and for those with developmental diseases,” adds Dr. Ishibashi. “But they’ve never been used to treat the brains of infants with congenital heart disease. That’s why we are trying to understand how well this system might work for our patient population.”

Dr. Ishibashi says the research team will focus on three areas during their four-year study – whether the stem cells:

  • Reduce neurological inflammation,
  • Reverse or halt injury to the brain’s white matter and
  • Help promote neurogenesis in the subventricular zone, the largest niche in the brain for creating the neural stem/progenitor cells leading to cortical growth in the developing brain.

At the conclusion of the research study, Dr. Ishibashi says the hope is to develop robust data so that someday an effective treatment will be available and lasting neurological damage in infants with congenital heart disease will become a thing of the past.

Femoral fracture

POSNA grant addresses variations in femoral fracture treatment

Femoral fracture

While there are plenty of options for treating pediatric femoral diaphyseal fractures, doctors don’t have a lot of specific guidance on the optimal regimen for each patient age, fracture location and fracture pattern.

Pediatric femoral diaphyseal fractures are some of the most common types of long bone fractures. There are many effective ways to treat these injuries, but unfortunately this assortment of options also leads to variations in cost and clinical outcome for patients and makes it difficult to develop clinical trials exploring the treatment of pediatric femur fractures.

To address this issue, a Children’s National research team led by Matthew Oetgen, M.D., M.B.A., Division Chief of Orthopaedic Surgery and Sports Medicine, received a $30,000 grant from the Pediatric Orthopaedic Society of North America (POSNA) to design a multi-centered, randomized, controlled clinical trial for the treatment of pediatric diaphyseal femur fractures. The team’s ultimate goal is to submit the resulting trial design to an extramural agency for study funding.

While there are plenty of options for treating pediatric femoral diaphyseal fractures, doctors don’t have a lot of specific guidance on the optimal regimen for each patient age, fracture location and fracture pattern. As a result, many treatment decisions are based on surgeon preference, regional variation in care and previous training or experience.

Another issue that arises in the treatment of diaphyseal femur fractures is the impact on the patient’s family. In general, femur fractures are caused by significant trauma that affects both the patient and the family members. On top of this, families are faced with issues such as extended hospitalization, the need for wheelchairs and walkers, pain control, missed school and secondary surgeries for removal of implants. Often, families are left to their own devices to resolve these issues, many of which are more impactful than the injury itself.

Dr. Oetgen believes that a well-planned and well-structured randomized clinical trial guided by patient and family concerns as well as expert surgical opinion has the potential to improve both treatment and care of femoral diaphyseal fracture patients.

“It is no longer good enough to design studies that only look at healing time for femur fractures,” explains Dr. Oetgen. “These injuries have such significant secondary impacts for the families of these patients, we need to determine which treatment is optimal for both fracture healing and is easiest for the families to tolerate. This grant will allow us to consider all of these outcomes in designing a study to find the best treatment for these injuries.”

To aid in the design of their clinical trial, Dr. Oetgen and his team will:

  1. Conduct an extensive literature review on the impact and treatment of pediatric femur fractures.
  2. Survey a diverse group of pediatric orthopaedic surgeons to establish areas of agreement, opposition and equipoise on the surgical treatment of pediatric femur fractures, and use that information to form a consensus opinion on the optimal design of the clinical trial.
  3. Solicit input from non-physician stakeholders (families, parents, payers, state Medicaid representatives, patient advocacy groups, professional organizations) on the important aspects of care in pediatric femur fracture treatment.

The team expects to have the study design competed by February 2019.

Children’s National Health System advances sickle cell disease cure through Doris Duke Charitable Foundation grant


An innovative Children’s National Health System project aimed at improving the only proven cure for sickle cell disease – hematopoietic cell transplantation – will receive more than $550,000 in funding from the Doris Duke Charitable Foundation’s inaugural Sickle Cell Disease/Advancing Cures Awards, which provides grants to advance curative approaches for sickle cell disease. The study, a three-year, multi-center trial that will study a low intensity, chemotherapy-free transplantation approach to cure children with sickle cell disease using a matched related donor, is led by Allistair Abraham, M.D., blood and marrow transplantation specialist, and Robert Nickel, M.D., hematologist, and is one of seven projects receiving approximately $6 million total through the awards.

While transplantation using a matched sibling donor today has a high cure rate (>90 percent) for sickle cell disease, traditional transplant approaches have many risks and side effects in both the short and long term. The study will examine if a chemotherapy-free approach can lead to a successful transplant without resulting in graft-versus-host disease (GVHD). GVHD is one of the most challenging complications of a transplant, in which the transplant immune cells attack the patient’s body. The researchers anticipate that this new transplant approach will be so well tolerated that patients’ quality of life will be maintained and improved throughout the process, with most of the care administered in a clinic setting.

“This approach has proven to be effective for adults with sickle cell disease, so we are grateful for the opportunity to begin this important trial for children thanks to the Doris Duke Charitable Foundation,” says Dr. Abraham. “Children with sickle cell disease are in need of innovative treatments, and we look forward to finding more solutions that improve the quality of life for these patients.”

“Advancing treatment for sickle cell patients to the point where they can live free of the disease is our top priority,” says Dr. Nickel, who is also an assistant professor of pediatrics at the George Washington University School of Medicine and Health Sciences. “This funding is critical to our study and it will accelerate the timeline to achieve the goal of a well-tolerated and safe cure for children with sickle cell disease.”

Matthew Hsieh, M.D., who helped pioneer this work at the National Institute of Health in adults, and Greg Guilcher, M.D., who has used this transplant approach in children, are key collaborators on the project.

The study is projected to begin in December 2018 and continue for three years. The Comprehensive Sickle Cell Disease Program at Children’s National is among the largest in the country, treating more than 1,400 children and young adults with all types of sickle cell disease. Children’s National also offers the largest, most comprehensive blood disorders team in the Washington, D.C., area.

Javad Nazarian

Advancing pediatric cancer research by easing access to data

Javad Nazarian

“This is a tremendous opportunity for children and families whose lives have been forever altered by pediatric cancers,” says Javad Nazarian, Ph.D., M.S.C., principal investigator in the Center for Genetic Medicine Research and scientific director of the Brain Tumor Institute at Children’s National.

Speeding research into pediatric cancers and other diseases relies not only on collecting good data, but making them accessible to research teams around the world to analyze and build on. Both efforts take time, hard work and a significant amount of financial resources – the latter which can often be difficult to attain.

In a move that could considerably advance the field of pediatric cancer, the National Institutes of Health (NIH), a body that funds biomedical research in the United States, recently awarded a public-private research collective that includes Children’s National Health System up to $14.8 million to launch a data resource center for cancer researchers around the world in order to accelerate the discovery of novel treatments for childhood tumors. Contingent on available funds, five years of funding will be provided by the NIH Common Fund Gabriella Miller Kids First Pediatric Research Program, named after Gabriella Miller, a 10-year-old child treated at Children’s National.

As principal investigators, researchers at Children’s Hospital of Philadelphia will lead the joint effort to build out the “Kids First” Data Resource Center. Children’s National in Washington, D.C., will spearhead specific projects, including the Open DIPG project, and as project ambassador will cultivate additional partnerships with public and private foundations and related research consortia to expand a growing trove of data about pediatric cancers and birth defects.

“This is a tremendous opportunity for children and families whose lives have been forever altered by pediatric cancers,” says Javad Nazarian, Ph.D., M.S.C., principal investigator in the Center for Genetic Medicine Research and scientific director of the Brain Tumor Institute at Children’s National. “From just a dozen samples seven years ago, Children’s National has amassed one of the nation’s largest tumor biorepositories funded, in large part, by small foundations. Meanwhile, research teams have been sequencing data from samples here and around the world. With this infusion of federal funding, we are poised to turn these data into insights and to translate those research findings into effective treatments.”

Today’s NIH grant builds on previous funding that Congress provided to the NIH Common Fund to underwrite research into structural birth defects and pediatric cancers. In the first phase, so-called X01 grantees—including Eric Vilain, M.D., Ph.D., newly named director of the Center for Genetic Medicine Research at Children’s National—received funding to sequence genetic data from thousands of patients and families affected by childhood cancer and structural birth defects.

This new phase of funding is aimed at opening access to those genetic sequences to a broader group of investigators around the globe by making hard-to-access data easily available on the cloud. The first project funded will be Open DIPG, run by Nazarian, a single disease prototype demonstrating how the new data resource center would work for multiple ailments.

DIPG stands for diffuse intrinsic pontine glioma, aggressive pediatric brain tumors that defy treatment and are almost always fatal. Just as crowd sourcing can unleash the collective brainpower of a large group to untangle a problem swiftly, open data sharing could accomplish the same for childhood cancers, including DIPG. In addition to teasing out molecular alterations responsible for making such cancers particularly lethal, pooling data that now sits in silos could help to identify beneficial mutations that allow some children to survive months or years longer than others.

“It’s a question of numbers,” Dr. Vilain says. “The bottom line is that making sense of the genomic information is significantly increased by working through large consortia because they provide access to many more patients with the disease. What is complicated about genetics is we all have genetic variations. The challenge we face is teasing apart regular genetic variations from those genetic variations that actually cause childhood cancers, including DIPG.”

Nazarian predicts some of the early steps for the research consortium will be deciding nuts-and-bolts questions faced by such a start-up venture, such as the best methods to provide data access, corralling the resources needed to store massive amounts of data, and providing data access and cross correlation.

“One of the major challenges that the data resource center will face is to rapidly establish physical data storage space to store all of the data,” Nazarian says. “We’re talking about several petabytes—1,000 terabytes— of data. The second challenge to address will be data dissemination and, specifically, correlation of data across platforms representing different molecular profiles (genome versus proteome, for example). This is just the beginning, and it is fantastic to see a combination of public and private resources in answering these challenges.”

FSH Society awards grant to Yi-Wen Chen

The FSH Society has awarded the FSH Society Grant FSHS-82016-4 to Children’s National researcher Yi-Wen Chen, D.M.V., Ph.D., to study facioscapulohumeral muscular dystrophy (FSHD).

Chen, Principal Investigator at the Center for Genetic Medicine Research at Children’s National and associate professor of pediatrics and integrative systems biology at George Washington University, will receive the research grant of $179,104 for two years for her project titled “Developing LNA-based therapy for facioscapulohumeral muscular dystrophy.”

FSHD is a complex genetic disorder caused by aberrantly expressed double homeobox protein 4 (DUX4) in patients’ cells that ultimately leads to the weakening of skeletal muscles often beginning in teenage years or early adulthood. Her research will focus on the next phases of developing LNA-based therapy for patients with FSHD through an in vivo study in a preclinical model.

“We have been designing compounds to inject into a preclinical model of FSHD in order to first reduce the DUX4 in the muscle and then identify the compounds that work best,” says Chen. Researchers will inject varying doses of the compound directly into the muscle for localized delivery and under the skin to reach the entire body for systemic delivery.

Currently there is no treatment for FSHD. After 15 years spent researching the disease, Chen hopes to test the efficacy of the compounds in order to identify a treatment.

Patrick Hanley receives prestigious Manasevit Research Scholar Grant

Patrick Hanley, Ph.D

Patrick Hanley, Ph.D., will receive the award at the ASBMT national meeting in late February 2017.

The American Society of Blood and Marrow Transplantation and the National Marrow Donor Program have awarded the Amy Strelzer Manasevit Research Scholar grant award to Children’s National researcher Patrick J. Hanley.

Hanley, Ph.D., Laboratory Facility Director, Cellular Therapy and Stem Cell Processing and Assistant Professor of Pediatrics at The George Washington University, will receive the award at ASBMT national meeting in late February 2017. It is the first time a Children’s National staff member has been awarded this grant, which is for $240,000 over three years.

The Amy research program is one of the largest and most coveted research grants in the field of marrow and cord blood transplantation, according to the program’s website.

“The program develops the next generation of physician-scientists by supporting and encouraging the discovery of new ways to treat and prevent post-transplant complications,” the program reports.

Hanley plans to use the grant to treat patients on their upcoming clinical trial, “CHEERS”, which is for patients receiving a cord blood transplant. These patients will receive immune cells that were expanded from cord blood, called T cells, that have been trained in the lab to target viruses – a major complication after transplant.

“This grant enables us to evaluate whether cord blood T cells that recognize viruses like CMV and now BK virus can offer protection to patients who need it most,” Hanley says.

Learn more about the grant program.

Muscular Dystrophy Association awards grants to two Children’s National scientists

Marshall Hogarth, Ph.D

Marshall Hogarth, Ph.D

James Novak, Ph.D.

James Novak, Ph.D.

Two Children’s National Health System research scientists, Marshall Hogarth, Ph.D. and James Novak, Ph.D., have received Post-Doctoral Development Grants from the Muscular Dystrophy Association (MDA) as part of funding awarded to young, rising researchers who are poised to become independent investigators.

Over the next three years, Hogarth and Novak will be allotted $180,000 each to underwrite their individual research projects.

Hogarth’s research is focused on limb-girdle muscular dystrophy (LGMD), a disease which presents as muscle weakness when patients are in their late teens before rapidly progressing to severe debilitation. The MDA grant will allow Hogarth to continue his research investigating the replacement of muscle with fatty tissue and the role this plays in the late onset and subsequent progression of LGMD in patients.

Novak focuses mainly on researching Duchenne Muscular Dystrophy (DMD), a severely debilitating form of MD, that leads to progressive muscle weakness and respiratory and cardiac failure. Currently, the only Food and  Drug Administration (FDA)  approved treatment for DMD is exon-skipping. The MDA grant will support Novak’s study of the mechanisms that regulate the delivery of exon-skipping drugs in muscle, in order to identify new therapeutic targets and improve drug efficacy for patients with DMD.

While Hogarth and Novak focus on different aspects of neuromuscular disease, both look forward to making significant contributions that lead to overall improvements in the treatment of patients impacted by muscular dystrophy.

Children’s receives $3M research grant from Mallinckrodt

Mallinckrodt Pharmaceuticals has awarded a $3 million Healthcare Advancement Grant to Children’s National Health System, supporting a research initiative focused on pediatric patients in the intensive care setting.

In the U.S., 20 percent of hospitalized children are cared for in the pediatric intensive care unit (ICU). Yet this is an under-researched patient population with layers of complexity. These patients face a 2.5 to 5 percent mortality rate, with 5 to 10 percent serious morbidity rate, and the morbidity and mortality rates double within three years.

Children’s National is uniquely qualified to address this opportunity, with its level IV neonatal ICU, ranked third in the nation by U.S. News and World Report in its 2016-2017 Best Children’s Hospitals survey. Home to the Children’s Research Institute and the Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National is one of the nation’s top National Institute of Health (NIH)-funded pediatric institutions. It is a member of the Collaborative Pediatric Critical Care Research Network of the NIH and enjoys strong partnerships with major universities in the Washington, DC, area, providing data-generation resources. The institution plans to mine data from this myriad of sources and more to unearth knowledge and improve outcomes.

Children’s National has identified three priorities to launch and execute this multi-year initiative, specifically:

  • Establish a Critical Care Outcomes Research Initiative team
  • Build on existing partnerships and expand to acquire additional data
  • Build outcomes research studies in the critical care arena

“We applaud Mallinckrodt for their forward thinking as we begin this important research initiative that will help meet the challenges faced by seriously ill pediatric patients,” said Robin Steinhorn, M.D., Senior Vice President for the Center for Hospital-Based Specialties. “We firmly believe the combination of this generous research grant, our many collaborative relationships and Children’s National’s renowned research enterprise will lead to improved outcomes for children in the future.”

Elena Grant

Interventional cardiac magnetic resonance team welcomes new specialist


The Interventional Cardiac Magnetic Resonance (ICMR) Program at Children’s National is actively developing newer and safer ways to perform cardiac procedures on young patients, with some of the world’s leading experts in cardiac catheterization and imaging. Elena Grant, M.D., a former pediatric cardiology fellow at Children’s National, is the newest member to join the team that pioneered real-time MRI-guided radiation-free cardiac catheterization for children.

In addition to clinical work as a Children’s National Interventional Cardiologist, Dr. Grant will perform preclinical research at the National Institutes of Health to develop new procedures, techniques, and devices that can be translated to clinical practice to treat children and adults with congenital heart disease.

Dr. Grant specializes in interventional cardiology. She received her medical degree from the University of Dundee Medical School in Dundee, Scotland, followed by Foundation Training in Edinburgh, Scotland. She completed her pediatric residency at Massachusetts General Hospital, her Pediatric Cardiology fellowship at Children’s National, and she recently finished an advanced fellowship in interventional pediatric cardiology at Children’s Healthcare of Atlanta and Emory University.

Advances in interventional cardiovascular MRI

Children’s National is at the forefront of this exciting new field and is currently the only institution in the United States to perform radiation-free MRI-guided cardiac catheterization procedures in children.

ICMR is a partnership with the National Institutes of Health that brings together researchers, clinicians, engineers, and physicists to provide radiation-free, less invasive, and more precise diagnostics and treatment options for pediatric patients and adults with congenital heart disease.

The ICMR approach to heart catheterization uses real-time MRI, instead of X-ray, in pediatric research subjects undergoing medically necessary heart catheterization. This research study is intended as a step toward routine MRI-guided catheterization in children, which attempts to avoid the hazards of ionizing radiation (X-ray).

In 2015, after working with NIH to explore how interventional cardiovascular MRI could be integrated into pediatric practices, the ICMR team, including Dr. Grant, Russell Cross, M.D., Joshua Kanter, M.D., and Laura Olivieri, M.D., performed the first  radiation-free MRI-guided right heart catheterization on a 14-year-old girl at Children’s National. Since then, nearly 50 such procedures have been successfully completed, and the team is working to broaden the age range and cardiac disease complexity of patients who can undergo the procedure.

About 1 percent of newborns are born with a heart condition, and the team at Children’s performs more than 450 X-ray guided cardiac catheterizations and over 500 cardiac MRI scans per year.