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girl with asthma inhaler

Children’s National becomes part of CAUSE Network

girl with asthma inhaler

Seven clinical sites in six different cities will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

The National Institute of Allergy and Infectious Diseases (NIAID) allocated $10 million in funding to establish the Childhood Asthma in the Urban Setting (CAUSE) network. The NIAID plans to increase this number by $70 million over seven years to support the network. Children’s National Hospital will be part of the new research network, which is a 7-year consortium comprising of seven clinical sites in six different cities that will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

Children’s National is the home of Improving Pediatric Asthma Care in the District of Colombia (IMPACT DC). The program focuses on research, care and advocacy to decrease asthma morbidity experienced by at-risk youth in the region while serving as a model program for the nation. NIAID gave an initial $3 million to IMPACT DC to conduct its own pilot study of anti-IgE therapy to prevent asthma exacerbations. Additional support for this and other studies will come from subcontracts from the CAUSE Coordinating Center at the University of Wisconsin in Madison.

“This new award allows IMPACT DC to remain part of one of the nation’s most prestigious pediatric asthma research consortia,” said Stephen Teach, M.D, M.P.H., chair for the Department of Pediatrics at George Washington University School of Medicine and Health Sciences. “It will allow us to both pursue an independent research agenda while collaborating with similar academic centers nationwide.”

Pediatric asthma is the most common chronic disease in children, and it is estimated that about 6.1 million children under 18 years suffer from this condition. It disproportionately affects urban, minority and under-resourced children and adolescents.

“It is essential to develop an understanding of the basic immunology of the disease and therapeutic options to ameliorating these disparities,” said Dr. Teach.

CAUSE researchers will explore the mechanisms of immune tolerance to allergens, the role of early environmental exposures in the pathogenesis of asthma, the pathogenesis and mechanisms of non-atopic asthma, the role of the respiratory epithelium in asthma and more.

The CAUSE network comprises of seven clinical research centers, including Children’s National led by principal investigator, Dr. Teach, and the following research centers:

  • Boston Children’s Hospital. Principal investigators: Wanda Phipatanakul, M.D., and Talal Chatila, M.D.
  • Cincinnati Children’s Hospital Medical Center. Principal investigator: Gurjit Khurana Hershey, M.D., Ph.D.
  • Columbia University Health Sciences, New York. Principal investigator: Meyer Kattan, M.D.
  • Icahn School of Medicine at Mount Sinai, New York. Principal investigators: Paula Busse, M.D., Supinda Bunyavanich, M.D., and Juan Wisnivesky, M.D.
  • Lurie Children’s Hospital of Chicago. Principal investigators: Rajesh Kumar, M.D., and Jacqueline Pongracic, M.D.
  • University of Colorado Denver. Principal investigator: Andrew Liu, M.D.
pregnant woman getting a checkup

Children’s National awarded $4.2 million to lead maternal mental health research programs

pregnant woman getting a checkup

Mothers and their babies often experience stress, depression and anxiety, which impacts the infant’s brain development.

Children’s National Hospital announces a $4.2 million funding award from the Patient-Centered Outcomes Research Institute (PCORI) to support maternal mental health research. The Developing Brain Institute at Children’s National will lead a new program that seeks to advance perinatal mental health and well-being while addressing racial disparities in access to resources that could boost positive health outcomes for women with few opportunities.

Mothers and their babies often experience stress, depression and anxiety, which impacts the infant’s brain development. Maternal psychological distress is more pronounced among low-income mothers — a health disparity that was exacerbated during the COVID-19 pandemic.

“The new fund will support many scientific research portfolios, including our project that will ensure pregnant women in D.C. get the care they need and deserve,” said Catherine Limperopoulos, Ph.D., director of The Developing Brain Institute at Children’s National and co-principal investigator of the project.

“I’m honored to be working alongside Dr. Limperopoulos and our partners. Collectively, our team aims to meet the needs of African American pregnant and postpartum women and their families during this important transition in their lives by providing services to address social determinants of health and prevent and treat maternal distress,” said Huynh-Nhu Le, Ph.D., the co-principal investigator of the project and professor in the Clinical Psychology program, part of the department of Psychological and Brain Sciences at George Washington University.

Cognitive-behavioral intervention, patient navigation and peer support, such tailored strategies developed in the program will provide effective mental health screening and care for 1,000 mothers living in Washington D.C. that is responsive to their cultural, social, environmental, behavioral and medical needs. The participants will access the resources either online or in-person, depending on the type of assistance that fits their lifestyle.

“I am overjoyed that PCORI has provided this essential funding, giving life to our project. The research done here will have a grand effect! Our goals are ambitious: To dissect all aspects of maternal health, beyond just mental health, literally creating a detailed timeline of events a mother can anticipate experiencing from pregnancy, at delivery and postpartum,” said Shanae Bond, one of the women whose firsthand experience giving birth in D.C. informed the study design. “With the maternal health crisis we are currently facing, it’s imperative to gain this type of insight to not only support mothers but to learn how they wish to be supported and how to best improve the care they receive – based on how it impacts, improves (or impairs) their lives,” said Bond.

The multidisciplinary group includes doctors, midwives, psychologists, advisors, community leaders and four prenatal care centers, MedStar Washington Hospital Center, Howard University, The George Washington University and Unity Health Care.

“Our initiative brings together obstetrics, pediatrics, and mental health care in an integrated care model. This collaboration brings early identification and immediate care coordination to its rightful place at the center of care,” said Loral Patchen, Ph.D., CNM, vice chair, Innovation and Community Programs at MedStar Washington Hospital Center. “The prenatal period offers an opportunity for us to support emotional healing, build coping strategies, and offer a safe space for people to prepare for the complex transitions that accompany childbearing. Offering services prior to delivery optimizes opportunity for strong parent-infant attachment and mitigates potential disruptions.”

Kristin L. Atkins, M.D., FACOG, assistant professor in the Obstetrics and Gynecology Department at Howard University College of Medicine, mentioned that Howard University is honored to partner with Children’s National Hospital. “The new program will help discover more about prenatal care interventions related to maternal mental health and how they may impact fetal and pediatric brain development,” said Dr. Atkins. “We are just discovering the impact of long-standing stress on health and well-being, and this starts in utero.”

To Jennifer Keller, M.D., MPH, FACOG, associate professor at The George Washington University School of Medicine & Health Sciences, this project is essential. “The events of the last year have had a profound impact on families in this city,” said Dr. Keller. “This project begins at a time of critical mental health needs for pregnant people in D.C.”

Siobhan Burke, M.D., director of OB/GYN at Unity Health Care, is also thrilled to be part of this partnership. “We all know underlying stressors such as financial difficulties, housing instability and systemic racism can impact health, but it’s important to find out what these things do to the developing fetus and to explore strategies to make lives better,” said Dr. Burke.

In 2020, Children’s National established The Clark Parent & Child Network funded by a $36 million investment from the A. James & Alice B. Clark Foundation. The Clark Network aims to provide families with greater access to mental health care and community resources. New projects like the D.C. mother-infant behavioral wellness program underwritten by PCORI funding will become natural extensions of this essential work.

“This project was selected for PCORI funding not only for its scientific merit and commitment to engaging patients and other stakeholders, but also for its potential to fill an important gap in our health knowledge and give people information to help them weigh the effectiveness of their care options,” said PCORI Executive Director Nakela L. Cook, M.D., M.P.H.. “We look forward to following the study’s progress and working with Children’s National Hospital to share the results.”

This $4.2 million PCORI funding has been approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.

 

Research & Innovation Campus

Virginia Tech, Children’s National Hospital award $100,000 to fund collaborative cancer research pilot projects

Research & Innovation Campus

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus.

Children’s National Hospital and Virginia Tech have awarded two $50,000 one-year pilot grants to multi-institutional teams of scientists for pediatric brain cancer research.

The inter-institutional program, which launched in December, promotes cross-disciplinary collaborations among researchers at both institutions. At Virginia Tech, the program is part of the Virginia Tech Cancer Research Alliance. Financial support for the program was provided by the Offices of the Physician-in-Chief and Chief Academic Officer at Children’s National, and by Virginia Tech’s Office of the Vice President for Health Sciences and Technology.

“We were delighted to see so many innovative and competitive research proposals for our first round of pilot grants in the area of brain cancer. By forging new research collaborations with our partners at Children’s National, we hope to make major strides in addressing one of the most common and devastating groups of cancers in children,” said Michael Friedlander, Virginia Tech’s vice president for health sciences and technology, and the executive director of the Fralin Biomedical Research Institute at VTC. “The pilot funding will bootstrap several programs to be able to acquire ongoing sustainable funding by providing the opportunity to test novel high impact ideas for new strategies for treating these disorders. There are simply too few good options for children in this space now and this partnership can change that for the better.”

The collaborative research initiative began through an agreement between the Fralin Biomedical Research Institute and the Children’s National Research Institute. The collaborative teams formed through a series of interactive discussions among Virginia Tech’s Cancer Research Alliance faculty members from the university’s Blacksburg and Roanoke campuses, and Children’s National’s neuro-oncology researchers.

“I am extremely excited by this collaboration between VT and CNH that is focused on pediatric brain tumors which is such an area of unmet need,” said Catherine Bollard, M.D., M.B.Ch.B.,, director of Children’s National’s Center for Cancer and Immunology Research. “I am confident that the funded proposals will soon advance our understanding of pediatric brain tumors and, more importantly, facilitate more joint efforts between two world-class institutions which is especially timely with the development of the Children’s National Research & Innovation Campus.”

Yanxin Pei, Ph.D., an assistant professor in the Center for Cancer Immunology Research at Children’s National, and Liwu Li, Ph.D., a professor of biological sciences in Virginia Tech’s College of Science, were awarded one of the pilot research grants to study how white blood cells called neutrophils are involved in metastatic MYC-driven medulloblastoma, an aggressive type of brain tumor in children that often resists conventional radiation and chemotherapies.

Yuan Zhu, Ph.D., the Gilbert Family Professor of Neurofibromatosis Research at Children’s National, and Susan Campbell, Ph.D., an assistant professor of animal and poultry sciences in Virginia Tech’s College of Agriculture and Life Sciences, were awarded funds to study glioma-induced seizures in mice with a genetic mutation that inhibits the production of P53, a key protein involved in suppressing cancer cell growth and division.

The successful applicants will receive funding starting this month and are expected to deliver preliminary data to support an extramural research application by 2024.

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus. It will be the first research and innovation campus in the nation focused on pediatrics when it opens later this year and will house newly recruited teams of pediatric brain cancer researchers.

Liwu Li, Yanxin Pei, Susan Campbell, and Yuan Zhu

Liwu Li, Ph.D., Yanxin Pei, Ph.D., Susan Campbell, Ph.D., and Yuan Zhu, Ph.D., were awarded funding through the new pilot research program.

feeding tubes

NIH grant funds development of pediatric feeding tube placement device

feeding tubes

A new grant will help to finalize development of the Pediatric PUMA-G System, the world’s first and only ultrasound-based procedure for placing feeding tubes into the stomach.

Researchers at Children’s National Hospital have received grant funding from the National Institute of Diabetes and Digestive and Kidney Diseases, within the National Institutes of Health (NIH), to finalize development of the Pediatric PUMA-G System, the world’s first and only ultrasound-based procedure for placing feeding tubes into the stomach. The funding will also support the first clinical trial of this technology in pediatric patients.

“Children’s National was chosen because we have a strong record of innovating pediatric devices and surgical procedures through the Sheikh Zayed Institute and we have a busy clinical interventional radiology service,” says Karun Sharma, M.D., Ph.D., director of Interventional Radiology and associate director of clinical translation at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National. “We are proud to be a part of this collaboration that will potentially help improve care of pediatric patients who cannot tolerate feeding by mouth.”

The feeding tubes are vital for children who cannot eat or swallow and require liquid nutrition (known as enteral feeding). Common feeding tube placement procedures for children may expose them to risks from invasive surgical tools or from ionizing radiation, which may lead to cancer in young patients at elevated rates. The PUMA-G System is less invasive and uses ultrasound to help physicians image the body during the procedure.

The grant, totaling $1.6M, will clinically evaluate the Pediatric PUMA-G System in collaboration with CoapTech, a biotechnology medical device company and two other premier pediatric medical centers — New York-Presbyterian Morgan Stanley Children’s Hospital and Children’s Hospital of Philadelphia.

depressed mom holding baby

New grant to help establish maternal mental health telehealth program

depressed mom holding baby

Children’s National has received a $76,000 grant from the Health Resources & Services Administration (HRSA) which will allow a cross-functional team of neonatologists and psychologists to establish a parental mental telehealth program.

Worldwide about 10% of pregnant women and 13% of women who have just given birth experience a mental health disorder, primarily depression, according to the World Health Organization.

“This is a topic that is quickly garnering attention but remains extremely underfunded,” says Lamia Soghier, M.D., F.A.A.P., C.H.S.E., medical director of the Neonatal Intensive Care Unit (NICU) at Children’s National Hospital. “We tend to focus on the babies but don’t pay enough attention to the parents.”

Dr. Soghier’s focus has been on NICU parents who experience postpartum mood and anxiety disorders (PMADs), often due to their uniquely stressful experiences.

“We have been screening on a small scale for many years and have noticed a 33-45% rate of postpartum depression symptoms in our NICU families,” she says.

Maternal mental disorders are treatable with effective screening and interventions. Children’s National has received a $76,000 grant from the Health Resources & Services Administration (HRSA) which will allow a cross-functional team of neonatologists and psychologists to establish a parental mental telehealth program to expand screening and provide diagnosis, therapy and counseling to NICU parents who experience postpartum mood and anxiety disorders.

Dr. Soghier, along with Ololade ‘Lola’ Okito, M.D., neonatologist at Children’s National, and Erin Sadler, Psy.D., psychologist in the Division of Psychology and Behavioral Health at Children’s National, discuss the importance of this work.

Q: Tell us more about the program you’re establishing.

A: Dr. Soghier: This program will allow us to hire a licensed psychologist who will see families both in the NICU and through follow-up telehealth visits. It provides a one-stop shop for our families, which is particularly important during the COVID-19 pandemic. The grant will also allow us to develop an iPad loaner program to give loaner iPads to low income families who do not have access to a device or to reliable internet services so that they can receive therapy at home.

Dr. Sadler: We’ll be examining how the implementation of these services can increase accessibility and reduce barriers that prevent assessment and initiation of crucial mental health services for at-risk mothers. Our partnerships will be key. Mothers experiencing barriers to participating in care services in the NICU will also have access to an in-house, licensed psychologist through telehealth services within the comfort of their homes. Families experiencing problems accessing telehealth technology due to economic limits would get the loaner iPad. We’re meeting our families where they are in order to provide these critical services.

Q: Why is grant funding to important in this space?

A: Dr. Okito: Access to perinatal mental health services is limited at the local and national levels, particularly for vulnerable parents of infants admitted to the NICU. Little is known about the effect of interventions to address depression and anxiety among NICU parents, and this grant will allow us to contribute to this very important area of research.

Dr. Sadler: It is not enough to recognize the health disparities that exist amongst communities in our nation. It is imperative that we’re able to explore and examine solutions that can aid in enhancing the equity of care for children and adults alike. As Dr. Okito mentions, there is little to no research available that looks at the feasibility of the support programs we intended to put in place. We hope to create a viable model that could be used to help NICU families across the country.

Q: How is Children’s National uniquely positioned to do this work?

A: Dr. Soghier: Healthy moms and healthy dads equal happy babies. That’s why we will be taking care of the family as a whole. This is truly family-centered care and at the heart of what Children’s National is all about.

Dr. Sadler: The Children’s National NICU team has an established postpartum depression screening program. Through the piloted work, staff have identified notable barriers to universal screening, access to perinatal mental health support and the impact of PMADs on parent engagement in newborn care.  As a result, Children’s National is uniquely positioned to directly address such barriers and provide specialized care.

Q: What excites you about this work?

A: Dr. Sadler: As a specialist in perinatal and infant mental health, I look forward to being able to demonstrate the lasting impact maternal mental health services can provide for not only newborns and their families, but for care providers as well. I am excited to have additional opportunities to advocate for the integration of perinatal and infant mental health in non-traditional spaces.

Dr. Okito: I am most excited about the potential to expand universal depression screening among NICU parents. Having done this work for the past three years, I know there are limitations in screening because we’ve only been able to screen parents that are at the patient’s bedside. More screening will lead to more parents getting the referrals and services that they need.

MRI of the patient's head close-up

Madison Berl, Ph.D., receives 2020 PERF award for Infrastructure/Registry Research

MRI of the patient's head close-up

The Pediatric Epilepsy Research Foundation Grant (PERF) has awarded Madison Berl, Ph.D., neuropsychologist at Children’s National Hospital, the 2020 PERF award for Infrastructure/Registry Research. The funds will support her work on researching neuropsychological outcomes of children being considered for pediatric epilepsy surgery.

This grant, which provides $200,000 of research funding, will allow Dr. Berl to systematically collect data outcomes and create robust prediction models that are critical to achieving precision medicine that allows for selecting the most effective surgical treatment for an individual child.

“While seizures are a critical outcome, there is increasing recognition that outcomes beyond seizure control is critical to children and their families when evaluating and treating the impact of epilepsy and its treatments,” said Dr. Berl.

Guidelines and consensus statements related to pediatric epilepsy surgery are uniformly lacking high quality published outcome data to support clinical decisions that impact likelihood of seizure freedom and optimizing outcomes beyond seizures (e.g., neuropsychological functioning, quality of life, improved sleep). Despite recognition of the need for standardized collection of data on a multi-institutional basis, the efforts that exist are limited in scope.

Moreover, as new techniques – such as laser ablation and brain stimulation – are approved for pediatric patients, there is little information available to determine which children will benefit from which intervention.

“This project fundamentally is a multi-site registry for epilepsy surgery outcomes,” Dr. Berl added.

“However, this type of infrastructure also fosters growth and active collaboration within a network of pediatric epilepsy clinicians. I am excited because if successful, this will be the start of long-term collaborative effort.”

cystic kidney disease

NIH $4 million grant funds new core center for childhood cystic kidney disease

cystic kidney disease

The University of Alabama at Birmingham (UAB), in collaboration with Children’s National Hospital has received a five-year, $4 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH) to create a core center for childhood cystic kidney disease (CCKDCC). The UAB-CCKDCC will conduct and facilitate research into the causes of and possible treatments for cystic kidney diseases, particularly those that present in childhood.

The UAB/Children’s National grant is a U54 center grant, an NIH funding mechanism to develop a multidisciplinary attack on a specific disease entity or biomedical problem area. With this grant, UAB joins with investigators at the University of Kansas and the University of Maryland-Baltimore as part of the NIH Polycystic Kidney Disease Research Resource Consortium. The NIH describes the consortium as a framework for effective collaboration to develop and share research resources, core services and expertise to support innovation in research related to polycystic kidney disease.

“Infants with childhood cystic kidney disease may develop kidney failure within a few years after birth and some need dialysis and kidney transplantation before they reach adulthood,” said Lisa Guay-Woodford, M.D., director of the Clinical and Translational Science Institute at Children’s National and co-director of the UAB-CCKDCC. “In many cases, the earlier the onset of symptoms, the more severe the outcome.”

“The intent is to accelerate the science and advance research into new therapies for cystic kidney disease through enhanced sharing of resources and the establishment of a robust research community,” said Bradley K. Yoder, Ph.D., professor and chair of the UAB Department of Cell, Developmental and Integrative Biology and co-director of the UAB-CCKDCC. “Childhood polycystic disease can be a devastating condition for children and their families.”

The UAB-CCKDCC will focus primarily on childhood polycystic kidney disease, a condition that affects about one in 20,000 infants in the United States. The center’s primary goals are:

  • Provide the Polycystic Kidney Disease Research Resource Consortium members with access to phenotypic, genetic and clinical information and biomaterials from CCKD patients
  • Analyze pathways involved in cyst pathogenesis through the generation of verified genetic model systems and biosensor/reporter systems
  • Assess the impact of patient variants on cystic disease proteins through generation and validation of innovative models
  • Provide ready access to biological materials from genetic CCKD models
  • Develop efficient pipelines for in vitro and in vivo preclinical testing of therapeutic compounds

Dr. Guay-Woodford is an internationally recognized pediatric nephrologist with a research program focused on identifying clinical and genetic factors involved in the pathogenesis of inherited renal disorders, most notably autosomal recessive polycystic kidney disease (ARPKD). Her laboratory has identified the disease-causing genes in several experimental models of recessive polycystic kidney disease and her group participated in the identification of the human ARPKD gene as part of an international consortium. In addition, her laboratory was the first to identify a candidate modifier gene for recessive polycystic kidney disease. For her contributions to the field, she was awarded the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease, given by the Polycystic Kidney Disease Foundation and the International Society of Nephrology.

glial cells

Dr. Nathan A. Smith receives $600,000 DOD ARO grant to study the role of glial cells in neural excitability and cognition

glial cells

Microglia are the resident immune cells of the central nervous system that have highly dynamic processes that continuously survey the brain’s microenvironment, making contact with both neurons and astrocytes.

In his pursuit to understand the function of neural circuits within the brain, Nathan A. Smith, M.S., Ph.D., principal investigator at Children’s National Hospital, is examining how specialized glial cells, known as astrocytes and microglia, work together to influence neural networks and potentially enhance neuro-cognition.

Dr. Smith has just secured a new $600,000 grant from the Department of Defense Army Research Laboratory to pursue cutting-edge experimental approaches to examine the role of astrocytes in Ca2+-dependent microglia modulation of synaptic activity. This project will enhance our understanding of neuronal excitability and cognition, and define a new role for microglia in these processes.

“Glia cells play an important role in modulating synaptic function via Ca2+-dependent mechanisms,” says Dr. Smith. “It’s time for these cells to receive recognition as active participants, rather than passive contributors, in fundamental neural processes.”

Dr. Smith and his laboratory at Children’s National Research Institute are using novel experimental models to study the dynamics underlying Ca2+-mediated microglia process extension and retraction to further our understanding of how microglia, astrocytes and neurons interact in the healthy brain.

“Completion of the proposed studies has the potential to redefine the role(s) of microglia in higher brain functions and highlight the significant contribution of these cells,” Dr. Smith says. “Most importantly, elucidating the mechanisms that underlie glial cell modulation of neural circuits will not only further our understanding of normal brain function but also open new avenues to developing more accurate computational models of neural circuits.”

Dr. Nathan Smith

Dr. Smith and his laboratory at Children’s National Research Institute are using novel experimental models to study the dynamics underlying Ca2+-mediated microglia process extension and retraction to further our understanding of how microglia, astrocytes and neurons interact in the healthy brain.

Microglia are the resident immune cells of the central nervous system that have highly dynamic processes that continuously survey the brain’s microenvironment, making contact with both neurons and astrocytes. However, because of our inability to directly monitor Ca2+ activity in microglia, very little is known about the intracellular Ca2+ dynamics in resting microglia and their role in surveillance and modulation of synaptic activity.

Dr. Smith’s research team and his use of cutting-edge technology are a perfect match with the Army’s new modernization priorities. Dr. Smith’s research program and the new Army’s initiatives will greatly benefit from each other and ultimately contribute to a better understanding of the human brain.

“This research will help address a major gap in our understanding of the roles that glial cells play in regulating the computations of the nervous system through their interactions with neurons, which could also inspire a new class of artificial neural network architectures,” said Dr. Frederick Gregory, program manager, Army Research Office, an element of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory.

The grant will begin on July 1, 2020, and will last over three years. Dr. Smith’s research is also supported by other grants, including awards from the NIH and the National Science Foundation.

“As Dr. Smith’s mentor, the ultimate joy for a mentor is to see his mentees follow their dreams and be recognized for their accomplishments,” said Vittorio Gallo, Ph.D., Chief Research Officer at Children’s National Hospital. “I couldn’t be prouder of Nathan, and I am fully confident that this new research grant will help him continue to grow an exceptional research program.”

Xanxin Pei

Dr. Yanxin Pei receives prestigious grant from V Foundation for Cancer Research

Xanxin Pei

When asked about this award, Dr. Pei noted “I am so deeply grateful to receive this support from the V Foundation for Cancer Research…I will use these resources to aid our goal of discovering new therapies to treat medulloblastoma.”

Yanxin Pei, Ph.D., assistant professor in the Brain Tumor Institute and the Children’s Research Institute at Children’s National Hospital in Washington, D.C., has recently been awarded a prestigious grant by the V Foundation for Cancer Research to support her groundbreaking work in finding new treatments for childhood medulloblastoma.

Dr. Pei, who joined Children’s National in 2014 after training in the Wechsler-Reya lab at the Sanford-Burnham Institute in La Jolla, CA, has focused her work on the biology of medulloblastoma, the most common malignant brain tumor in children, with a major emphasis on the study of the medulloblastoma subtype most resistant to treatment. Children with this form of medulloblastoma have less than a 30% chance of survival five years from their diagnosis.

Having already developed one of the most important mouse models of this disease, Dr. Pei’s present V Foundation for Cancer Research Award, which includes becoming a V scholar, will explore the role of metabolism in the development of metastasis in MYC-amplified medulloblastomas (the most virulent form of medulloblastoma).

The V Foundation for Cancer Research Award is one of a series of prestigious awards Dr. Pei has received over the past 18 months for her work, including an NIH-sponsored 5-year award (ROI) evaluating other aspects of medulloblastoma development and resistance to therapy, and grants from the Rally Foundation, the Meghan Rose Bradley Foundation and the Children’s Cancer Foundation.

When asked about this award, Dr. Pei noted “I am so deeply grateful to receive this support from the V Foundation for Cancer Research…I will use these resources to aid our goal of discovering new therapies to treat medulloblastoma.”

Her cutting-edge work is generating national and international attention and firmly places Dr. Pei as an international leader in medulloblastoma research.

Marius George Linguraru

Marius George Linguraru, D.Phil., M.A., M.Sc., awarded Department of Defense grant for Neurofibromatosis application development

Marius George Linguraru

Marius George Linguraru, D.Phil., M.A., M.Sc., is a principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, where he founded and directs the Precision Medical Imaging Laboratory. He’s an expert in quantitative imaging and artificial intelligence.

Marius George Linguraru, D.Phil., M.A., M.Sc., a principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National has been awarded a Congressionally Directed Medical Research Program (CDMRP) grant through the Department of Defense. This grant allows Dr. Linguraru to develop a novel quantitative MRI application that can inform treatment decisions by accurately identifying which children with Neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) are at risk of losing their vision.

This grant is part of the Neurofibromatosis Research Program of the CDMRP, which fills research gaps by funding high impact, high risk and high gain projects. Dr. Linguraru, who directs the Precision Medical Imaging Laboratory in the Sheikh Zayed Institute, is collaborating with the Gilbert Family Neurofibromatosis Institute and the Children’s Hospital of Philadelphia on this project.

An expert in quantitative imaging and artificial intelligence, Dr. Linguraru has published several peer-reviewed studies on NF1 and OPG, a tumor that develops in 20 percent of children with NF1. The OPG tumor can cause irreversible vision loss, leading to permanent disability in about 50 percent of children with the tumor. This project, titled “MRI Volumetrics for Risk Stratification of Vision Loss in Optic Pathway Gliomas Secondary to NF1” will provide doctors certainty when identifying which children with NF1-OPG will lose vision and when the vision loss will occur.

Dr. Linguraru and his team will validate the quantitative MRI application that they’re developing by studying children at 25 NF1 clinics from around the world. Doctors using the application, which will perform comprehensive measurements of the OPG tumor’s volume, shape and texture, will upload their patient’s MRI into Dr. Linguraru’s application. Using recent advances in quantitative image analysis and machine learning, the application will then definitively determine whether the child’s NF1-OPG is going to cause vision loss and therefore requires treatment.

This diagnosis can occur before visual acuity starts to decline, which provides an opportunity for early treatment in children at risk for vision loss. Dr. Linguraru believes that early diagnosis and treatment can help to avoid lifelong visual impairment for these patients while preventing unnecessary MRIs and aggressive chemotherapy in pediatric patients who are not at risk of vision loss.

Occurring in one in 3,000 to 4,000 live births, NF1 is a genetic condition that manifests in early childhood and is characterized by changes in skin coloring and the growth of tumors along nerves in the skin, brain and other parts of the body. It is unknown why the OPG tumor caused by NF1 only results in vision loss for 50 percent of children. Some children will sustain lifelong disability from their vision loss, despite receiving treatment for their tumor, likely because treatment was started late. In other instances, doctors are unknowingly treating NF1-OPGs that would never cause vision loss.

Dr. Linguraru and his team have already proven that their computer-based, quantitative imaging measures are more objective and reliable than the current clinical measures, enabling doctors to make earlier and more accurate diagnoses and develop optimal treatment plans.

baby cardioilogy patient

Researchers receive $2.5M grant to optimize brain development in babies with CHD

baby cardioilogy patient

Children’s National Health System researchers Richard Jonas, M.D., Catherine Bollard, M.B.Ch.B., M.D., and Nobuyuki Ishibashi, M.D., have been awarded a $2.5 million, three-year grant from the National Institutes of Health (NIH) to conduct a single-center clinical trial at Children’s National. The study will involve collaboration between the Children’s National Heart Institute, the Center for Cancer and Immunology Research, the Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

The goal of the study will be to optimize brain development in babies with congenital heart disease (CHD) who sometimes demonstrate delay in the development of cognitive and motor skills. This can be a result of multiple factors including altered prenatal oxygen delivery, brain blood flow and genetic factors associated with surgery including exposure to the heart lung machine.

The award will be used to complete three specific aims of a Phase 1 safety study as described in the NIH grant:

  • Aim 1: To determine the safety and feasibility of delivering allogeneic bone marrow derived mesenchymal stromal cell (BM-MSC) during heart surgery in young infants less than 3 months of age using the heart lung machine. The optimal safe dose will be determined.
  • Aim 2: To determine the impact of MSC infusion on brain structure using advanced neuroimaging and neurodevelopmental outcomes.
  • Aim 3: To determine differences in postoperative inflammatory and patho-physiological variables after MSC delivery in the infant with CHD.

“NIH supported studies in our laboratory have shown that MSC therapy may be extremely helpful in improving brain development in animal models after cardiac surgery,” says Dr. Ishibashi. “MSC infusion can help reduce inflammation including prolonged microglia activation that can occur during surgery that involves the heart lung machine.”

In addition the researchers’ studies have demonstrated that cell-based intervention can promote white matter regeneration through progenitor cells, restoring the neurogenic potential of the brain’s own stem cells that are highly important in early brain development.

The Phase 1 clinical trial is being implemented in two stages beginning with planning, regulatory documentation, training and product development. During the execution phase, the trial will focus on patient enrollment. Staff from the Cellular Therapy Laboratory, led by director Patrick Hanley, Ph.D., manufactured the BM-MSC at the Center for Cancer and Immunology Research, led by Dr. Bollard. The Advanced Pediatric Brain Imaging Laboratory, led by Catherine Limperopoulos, Ph.D., will perform MR imaging.

The phase 1 safety study will set the stage for a phase 2 effectiveness trial of this highly innovative MSC treatment aimed at reducing brain damage, minimizing neurodevelopmental disabilities and improving the postoperative course in children with CHD. The resulting improvement in developmental outcome and lessened behavioral impairment will be of enormous benefit to individuals with CHD.

NCC-PDI Pitch Winners

NCC-PDI announces medical device pitch winners

NCC-PDI Pitch Winners

Five pediatric medical device innovators each captured $50K in funding and access to a new pediatric device accelerator program in a competition hosted April 30, 2019 by National Capital Consortium for Pediatric Device Innovation that focused on orthopedic and spine devices. Clockwise from front left: Kolaleh Eskandanian, Children’s National Health System; Cristian Atria, nView Medical; John Barrett, Auctus Surgical Inc.; Paul Mraz, ApiFix; Dan Sands, AMB Surgical II; Anuradha Dayal, BabySteps, Children’s National Health System; Paul Grand, MedTech Innovator; (center) Bill Bentley, Robert E. Fischell Institute for Biomedical Devices, University of Maryland.

The National Capital Consortium for Pediatric Device Innovation (NCC-PDI) announced five winners of its “Make Your Medical Device Pitch for Kids!” competition held on April 30 at the University of Maryland. Each winner receives $50,000 in grant funding and gains access to the consortium’s first-of-its-kind “Pediatric Device Innovator Accelerator Program” led by MedTech Innovator.

NCC-PDI, one of five FDA Pediatric Device Consortia grant programs that support the development and commercialization of pediatric medical devices, is led by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System and the A. James Clark School of Engineering at the University of Maryland. The consortium recently added new accelerators BioHealth Innovation and MedTech Innovator and design firm partner, Smithwise.

A panel of 32 expert judges from business, healthcare, regulatory and legal sectors selected the winners based on the clinical significance and commercial feasibility of their medical devices for children. The competition focused solely on advancing care in the pediatric orthopedics and spine sector which the FDA identified as an emerging underserved specialty lacking innovation.

The competition winners are:

  • AMB Surgical, LLC, Dayton, Ohio – FLYTE, a device designed to reduce invasive and repetitive surgery in children and teens with orthopedic illnesses such as scoliosis and limb abnormalities
  • Auctus Surgical, Inc., San Francisco, Calif. – Auctus Surgical Dynamic Spinal Tethering System, a mechanism used to correct the scoliotic spine in pediatric patients through a tethering procedure
  • ApiFix Ltd, Boston, Mass. – ApiFix’s Minimally Invasive Deformity Correction (MID-C) System, a posterior dynamic deformity correction system for surgical treatment to provide permanent spinal curve correction while retaining flexibility
  • Children’s National Health System, Washington, D.C.– Babysteps platform to improve initial assessment of clubfoot deformity and predict the magnitude of correction
  • nView Medical, Salt Lake City, Utah – Surgical scanner using AI-based image creation to provide instant 3D imaging during surgery to improve imagery speed and accuracy

“All finalists are winners and we believe that, with NCC-PDI’s support, some of the awarded devices will be available to orthopedic and spine clinicians in the near future. That is vitally important since innovation has been stagnant in this area,” says Kolaleh Eskandanian, Ph.D., MBA, PMP, vice president and chief innovation officer at Children’s National and principal investigator of NCC-PDI. “This competition aims to increase the profile of companies by exposing them to a panel of industry leaders who may become future investors or strategic partners.”

Through the inaugural NCC-PDI “Pediatric Device Innovator Accelerator Program,” MedTech Innovator is providing winners with virtual in-depth, customized mentorship from some of the industry’s leading executives and investors. MedTech Innovator has a proven track record of identifying early-stage medical device companies with the key characteristics required for commercial success and accelerating their growth through its vast ecosystem of resources.

“As a pediatric orthopedic surgeon, I am encouraged by the innovations presented at this competition,” says Matthew Oetgen, M.D., division chief of Orthopaedic Surgery and Sports Medicine at Children’s National, who served on the judging panel. “We need more devices that compensate for the smaller size of children compared to adults and that can adapt as children’s bones continue to grow and develop. The finalists who competed fully embraced that challenge.”

This was NCC-PDI’s eighth competition in six years and a ninth competition is planned for fall 2019 that focuses on NICU. Including this recent round of winners, the consortium has supported 94 pediatric medical devices and helped five companies receive FDA or CE mark regulatory clearance.

To learn more about the winners and the fall 2019 pitch competition, visit the National Capital Consortium for Pediatric Device Innovation website.

Steven Hardy

Steven Hardy, Ph.D., awarded prestigious NIH grant for sickle cell research, career development

Steven Hardy

Steven Hardy, Ph.D., a pediatric psychologist in the Center for Cancer and Blood Disorders at Children’s National, has been awarded a K23 Mentored Patient-Oriented Research Career Development Award by the National Heart, Lung, and Blood Institute (NHLBI) in recognition of his progress toward a productive, independent clinical research career. National Institutes of Health (NIH) Mentored Career Development Awards are designed to provide early career investigators with the time and support needed to focus on research and develop new research capabilities that will propel them to lead innovative studies in the future.

Dr. Hardy, who has worked at Children’s National since 2013, specializes in the emotional, behavioral and cognitive aspects of children’s health, with a particular emphasis on evaluating and treating psychological difficulties among children with cancer or sickle cell disease. With the K23 award, he will receive nearly $700,000 over a five-year period, which will provide him with an intensive, supervised, patient-oriented research experience. The grant will support Dr. Hardy’s time to conduct research, allow him to attend additional trainings to enhance research skills, and fund a research project titled “Trajectory of Cognitive Functioning in Youth with Sickle Cell Disease without Cerebral Infarction.”

Many children with sickle cell disease (SCD) also have intellectual challenges which stem from two primary pathways – stroke and other disease-related central nervous system effects. While stroke is a major complication of SCD, the majority of children with SCD have no evidence of stroke but may still exhibit cognitive functioning challenges related to their disease. Such cognitive difficulties have practical implications for the 100,000 individuals in the SCD, as 20-40% of youth with SCD repeat a grade in school and fewer than half of adults with SCD are employed. Dr. Hardy’s project will focus on understanding the scope and trajectory of cognitive difficulties in children with SCD without evidence of stroke, as well as the mechanisms that precipitate disease-related cognitive decline. The study will characterize temporal relationships between biomarkers of SCD severity and changes in cognitive functioning to inform future development of risk stratification algorithms to predict cognitive decline. Armed with the ability to predict cognitive decline, families will have additional information to weigh when making decisions and providers will be better able to intervene and tailor treatment.

young girl sitting on a bed with a cast

Creating better casts

young girl sitting on a bed with a cast

Each year, millions of children in the U.S. come to hospital emergency departments with fractures. While broken bones are commonplace, the expertise to stabilize these injuries and cast them is not, says Children’s National Health System orthopedic surgeon Shannon Kelly, M.D.

Most fractures are casted by an on-call resident without the assistance of an orthopedist, she explains. Whether that resident applies a cast successfully depends largely on how well he or she learned this skill as an intern. While most current training models have interns take calls with residents, picking up casting skills through hands-on experience from their more senior peers, they can also pick up mistakes – which get repeated once they’re caring for patients independently as residents themselves, Kelly says.

Casting mistakes aren’t trivial, she adds. They can have serious consequences for patients. For example, a cast that’s not tight enough in the right places can leave bones vulnerable to shifting, a scenario that doctors call a loss in reduction, Kelly explains. If bones aren’t in the right position to heal, doctors must reposition them either in the operating room, often exposing patients to general anesthesia, or through painful, in-office procedures.

Conversely, casts that are too tight – particularly on a fresh fracture that’s prone to swelling – can damage tissues from loss of circulation. To avoid this latter problem, doctors often create a “bivalve” cast in which the two halves are split like a clamshell, leaving room for tissues to expand. But they must use extreme care when they cut open the cast with a saw to avoid cutting patients with the rotating blade or burning them with heat generated from its friction.

“Each year, thousands of children are harmed from improper casting and must go through additional procedures to fix the damage done,” Kelly says.

That’s why she and her colleagues are developing a better way to train interns before they start their orthopedics rotation. Starting this spring, the team will be directing a series of casting workshops to train interns on the proper casting technique.

The workshops will take advantage of models that allow interns to practice without harming patients. Some of these models have simulated bones that show up on an X-ray, allowing participants to evaluate whether they achieved a good reduction once they’re finished. Other models are made of wax that melts if the heat of a cast saw becomes too intense and show nicks if the blade makes contact. Learning proper technique using this tool can help spare human patients painful burns and cuts, Kelly says.

To broaden this effort beyond Children’s National, Kelly and her colleagues received a $1,000 microgrant from the Pediatric Orthopaedic Society of North America to create videos based on material from these workshops. These videos will help trainees at medical institutions across the country learn the same pivotal casting skills.

“A broken bone is difficult enough,” Kelly says. “We’re hoping to decrease the number of times that a child has to have an unnecessary procedure on top of that from a casting mistake that could have been avoided.”

Yuan Zhu

The brain tumor field moves forward with new findings and a research grant

Yuan Zhu

Yuan Zhu, Ph.D., and other experts completed new research findings evaluating the effects of manipulating the growth-promoting signaling pathways in brain tumors associated with adults and children.

This month, experts at Children’s National Health System made great strides in brain tumor research, specifically in gliomas, glioblastomas and medulloblastomas. Led by Yuan Zhu, Ph.D., the scientific director and Gilbert Endowed Professor of the Gilbert Family Neurofibromatosis Institute and Center for Cancer and Immunology Research at Children’s National, the team completed new research findings evaluating the effects of manipulating the growth-promoting signaling pathways in brain tumors associated with adults and children. Dr. Zhu’s research was recently published in Cell Reports and he was also awarded a U.S. Department of Defense (DoD) grant to gain a better understanding of how low-grade gliomas form. Together, this work moves the needle on developing more effective treatments for these debilitating and life-threatening tumors.

The study

In his recently published paper, Dr. Zhu and his colleagues, including Drs. Seckin Akgul and Yinghua Li, studied glioblastomas, the most common brain tumor in adults, and medulloblastomas, the most common brain tumor found in children, in genetically engineered experimental models. Dr. Zhu found that when they removed the p53 gene (the most commonly mutated tumor suppressor gene in human cancers) in the experimental model’s brain, most developed malignant gliomas and glioblastomas, while Sonic Hedgehog (SHH)-subtype (SHH) medulloblastomas were also observed. They further suppressed the Rictor/mTorc2 molecular pathway that is known in the regulation of tumor growth. This action greatly reduced the incidence of malignant gliomas and extended the survival of the models, validating the concept that Rictor/mTorc2 could be a viable drug target for this lethal brain cancer in adults.

The study also found that the same Rictor/mTorc2 molecular pathway serves the opposite function in SHH medulloblastoma formation, acting as a tumor suppressor. Findings suggest that if the same drug treatment is used for treating SHH medulloblastoma in children, it could potentially have an adverse effect and promote growth of the tumors.

Ultimately, the study demonstrates that Rictor/mTORC2 has opposing functions in glioblastomas in adults and SHH medulloblastomas in children. While drug therapies targeting Rictor/mTORC2 may be successful in adults, the findings reveal the risks of treating children with pediatric brain tumors when using the same therapies.

The grant

Continuing the study of brain tumors, Dr. Zhu recently received a $575,000 grant from DoD to research benign gliomas, with the hope of gaining a greater understanding of how the tumors form. Low-grade gliomas, or benign brain tumors, are the most common brain tumors in children. While not lethal like their high-grade counterpart, these tumors can lead to significant neurological defects, permanently impacting a child’s quality of life. Most commonly, the tumor can impair vision, often leading to blindness.

Since the tumors only occur in children under the age of eight, Dr. Zhu believes they are linked to neural stem or progenitor cells that exist in the optic nerve only during development, or when children are under eight-years-old. To test if his hypothesis is correct, Dr. Zhu will develop a preclinical model that mimics human brain tumors to study the development of the optic nerve. If his theory proves correct, Dr. Zhu’s long-term goal is to develop a strategy that prevents the tumor formation from ever occurring, ultimately preventing vision loss in children. The grant begins in July and will run for three years.

 

Doctors-working-with-Digital-Tablet

New network will advance treatments for children

Doctors-working-with-Digital-Tablet

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

Sickle-Cell-Blood-Cells

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.”