Genetics & Rare Diseases

Motor neuron connecting to muscle fiber

FDA approves muscular dystrophy drug built on Children’s National research

Motor neuron connecting to muscle fiber

Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease.

Boys with Duchenne muscular dystrophy (DMD) have a clinically proven, new treatment option with the Food and Drug Administration’s approval of vamorolone, a steroidal-type, anti-inflammatory drug developed based on research performed at Children’s National Hospital.

Created by ReveraGen BioPharma Inc., vamorolone has a molecular structure similar to traditional corticosteroids, which are currently used to treat DMD. Yet its structure was found to be chemically different enough to reduce unwanted side effects, including brittle bones and reduced stature. Nearly two decades ago, ReveraGen leaders – President and CEO Eric Hoffman, Ph.D., and Vice President for Research Kanneboyina Nagaraju, D.V.M., Ph.D. – launched research efforts into the drug when they led the Center for Genetic Medicine Research at Children’s National. They worked with then-Chief Academic Officer Mark Batshaw, M.D., on the new clinical option.

“Throughout my career, I have treated children with DMD, and I have seen over time how their shorter heights and brittle bones impact them physically and emotionally – in terms of their self-esteem and ability to participate in activities,” Dr. Batshaw said. “This drug should help these boys function more effectively and prevent certain long-term complications.”

The patient benefit

Muscular dystrophy includes a group of degenerative genetically inherited neuro-muscular diseases that strike only boys. DMD is the most common, severe and life-threatening form of muscular dystrophy. ReveraGen studied vamorolone for patients ages two years and up in the hopes of providing a new, FDA-approved treatment option for these children. In clinical trials, daily treatment with vamorolone improved muscle strength and stature with results comparable to prednisolone, but without some of the most impactful side effects of steroids, particularly the stunted growth and weakened bones.

Children’s National Hospital leads the way

Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer for Children’s National, said Drs. Hoffman and Nagaraju’s work on the drug paved the way for entrepreneurship at the hospital, as they were the first faculty members to launch a spin-off company. Since then, more than 130 faculty members have been named as inventors on 132 patents. Children’s National is now home to Innovation Ventures, the hospital’s intellectual property development and commercialization arm, which provides guidance and resources to academic entrepreneurs who introduce a concept for pediatric medical products.

“We cannot wait to see the tremendous effort behind vamorolone in the hands of patients and clinicians treating Duchenne muscular dystrophy,” Eskandanian said. “Today’s FDA approval for ReveraGen shows the importance of supporting clinicians and researchers who are developing solutions to advance healthcare for children.”

Why we’re excited

Hoffman said the drug has been through a series of clinical trials showing advantages over the current treatment options. In 2024, Catalyst Pharma will market vamorolone under the trade name Agamree in the United States.

“Vamorolone was developed using a different business model and drug development approach, including partnerships with the National Institutes of Health, Department of Defense, the European Commission and more than a dozen international nonprofit foundations,” Dr. Hoffman said. “The collaborative, community-engaged approach—including 32 academic clinical sites in 11 countries — and the participation of hundreds of DMD families led to this approval today.”

Patient and doctor demoing Rare-CAP technology

M.D. in your pocket: New platform allows rare disease patients to carry medical advice everywhere

When someone has a rare disease, a trip to the emergency room can be a daunting experience: Patients and their caregivers must share the particulars of their illness or injury, with the added burden of downloading a non-specialist on the details of a rare diagnosis that may change treatment decisions.

Innovators at Children’s National Hospital and Vanderbilt University Medical Center, supported by Takeda, are trying to simplify that experience using a new web-based platform called the Rare Disease Clinical Activity Protocols, or Rare-CAP. This revolutionary collection of medical information allows patients to carry the latest research-based guidance about their rare disorders in their phones, providing a simple QR code that can open a trove of considerations for any medical provider to evaluate as they work through treatment options for someone with an underlying rare disease.

“No one should worry about what happens when they need medical help, especially patients with rare diseases,” said Debra Regier, M.D., division chief of Genetics and Metabolism at Children’s National and Rare-CAP’s lead medical advisor. “We built this new tool because I have watched as my patient-families have wound up in an emergency room — after all, kids get sprains or fractures — but they don’t have the expertise of a rare disease specialist with them. My hope is that they’re going to pull out their phones and access Rare-CAP, which will explain their rare disease to a new provider who can provide more thoughtful and meaningful care.”

The big picture

A rare disease is defined as any disorder that affects less than 200,000 people in the United States. Some 30 million Americans are believed to be living with one of the 7,000 known rare disorders tracked by the National Organization of Rare Diseases (NORD). Led by Dr. Regier, the Rare Disease Institute at Children’s National is one of 40 NORD centers for excellence in the country that provide care, guidance and leadership for the wide array of disorders that make up the rare disease community.

While a key goal of Rare-CAP is to bolster patient self-advocacy, the platform will also allow medical providers to proactively search for protocols on rare diseases when they know they need specialized advice from experts at Children’s National, a network of tertiary care centers and patient organizations.

As a leading values-based, R&D-driven biopharmaceutical company, Takeda has committed $3.85 million to the project to help activate meaningful change and empower a brighter future for rare disease communities, providing a unique understanding of the struggle that patients and caregivers face when they need care.

“Our team, alongside the medical and rare disease community, saw the need for a single portal to collect standardized care protocols, and we are thrilled to see this innovative tool come to life,” said Tom Koutsavlis, M.D., head of U.S. Medical Affairs at Takeda. “People with rare diseases and their caregivers need faster access to authoritative medical information that providers anywhere can act on, this will lead to improving the standard of care, accelerating time to diagnosis and breaking down barriers to increase equitable access.”

The patient benefit

The creators of Rare-CAP imagined its use in a wide range of settings, including emergency rooms, surgical suites, dental offices, urgent care offices and school clinics. The platform will eventually profile thousands of rare diseases and lay out the implications for care, while also creating a dynamic conversation among users who can offer updates based on real-world experience and changes in medical guidance.

“Our patients are unique, and so is this tool,” Dr. Regier said. “As we roll out Rare-CAP, we believe it is just the beginning of the conversation to expand the platform and see its power for the patient and provider grow, with each entry and each new rare disease that’s added to the conversation.”

Catherine Limperopoulos

Imaging reveals altered brain chemistry of babies with CHD

Researchers at Children’s National Hospital used magnetic resonance spectroscopy to find new biomarkers that reveal how congenital heart disease (CHD) changes an unborn baby’s brain chemistry, providing early clues that could someday guide treatment decisions for babies facing lifelong health challenges.

Published in the Journal of the American College of Cardiology, the findings detail the ways that heart defects disrupt metabolic processes in the developing brain, especially during the third trimester of pregnancy when babies grow exponentially.

“Over the past decade, our team has been at the forefront of developing safe and sophisticated ways to measure and monitor fetal brain health in the womb,” said Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal and Maternal Health Research at Children’s National. “By tapping into the power of advanced imaging, we were able to measure certain maturational components of the brain to find early biomarkers for newborns who are going to struggle immediately after birth.”

The fine print

In one of the largest cohorts of CHD patients assembled to date, researchers at Children’s National studied the developing brains of 221 healthy unborn babies and 112 with CHD using magnetic resonance spectroscopy, a noninvasive diagnostic test that can examine chemical changes in the brain. They found:

  • Those with CHD had higher levels of choline and lower levels of N-Acetyl aspartate-to-choline ratios compared to healthy babies, potentially representing disrupted brain development.
  • Babies with more complex CHD also had higher levels of cerebral lactate compared to babies with two ventricle CHD. Lactate, in particular, is a worrying signal of oxygen deprivation.

Specifically, elevated lactate levels were notably increased in babies with two types of heart defects: transposition of the great arteries, a birth defect in which the two main arteries carrying blood from the heart are switched in position, and single ventricle CHD, a birth defect causing one chamber to be smaller, underdeveloped or missing a valve. These critical heart defects generally require babies to undergo heart surgery not long after birth. The elevated lactate levels also were associated with an increased risk of death, highlighting the urgency needed for timely and effective interventions.

The research suggests that this type of imaging can provide a roadmap for further investigation and hope that medicine will someday be able to better plan for the care of these children immediately after their delivery. “With important clues about how a fetus is growing and developing, we can provide better care to help these children not only survive, but thrive, in the newborn period and beyond,” said Nickie Andescavage, M.D., Children’s National neonatologist and first author on the paper.

The big picture

CHD is the most common birth defect in the United States, affecting about 1% of all children born or roughly 40,000 babies each year. While these defects can be fatal, babies who survive are known to be at significantly higher risk of lifelong neurological deficits, including lower cognitive function, poor social interaction, inattention and impulsivity. The impact can also be felt in other organ systems because their hearts did not pump blood efficiently to support development.

Yet researchers are only beginning to pinpoint the biomarkers that can provide information about which babies are going to struggle most and require higher levels of care. The National Institutes of Health (NIH) and the District of Columbia Intellectual and Developmental Disabilities Research Center supported the research at Children’s National to improve this understanding.

“For many years we have known that the brains of children with severe heart problems do not always develop normally, but new research shows that abnormal function occurs already in the fetus,” said Kathleen N. Fenton, M.D., M.S., chief of the Advanced Technologies and Surgery Branch in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). “Understanding how the development and function of the brain is already different before a baby with a heart defect is born will help us to intervene with personal treatment as early as possible, perhaps even prenatally, and improve outcomes.”

Note: This research and content are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The NIH provided support for this research through NHLBI grant R01HL116585 and the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant P50HD105328.

AAP conference logo

Children’s National Hospital at the 2023 American Academy of Pediatrics meeting

There will be over 20 Children’s National Hospital-affiliated participants at this year’s American Academy of Pediatrics National Conference and Exhibition. The meeting will take place in Washington, D.C., from October 20 – October 24. We have compiled their sessions into a mini schedule below.

 

Date Time Presenter Title Division
10/20/2023 8:30 AM Vanessa Madrigal, M.D., M.S.C.E. Section on Cardiology & Cardiac Surgery Program: Day 1 Critical Care
10/20/2023 2:30 PM Kibileri Williams, M.B.B.S Appy Hour: a Current Update on Pediatric Appendicitis Surgery
10/20/2023 3:30 PM Roopa Kanakatti Shankar, M.D., M.S. Precocious Puberty: Puberty Suppression or Not? Endocrinology
10/21/2023 7:30 AM Allison Markowsky, M.D. What is Trending in the Newborn Nursery: Controversies and Evidence Hospital Medicine
10/21/2023 8:00 AM Jessica Herstek, M.D. Joint Program: Council on Clinical Information Technology and Council on Quality Improvement and Patient Safety Medical Informatics
10/21/2023 8:00 AM Nazrat Mirza, M.D., Sc.D. Section on Obesity Program IDEAL Clinic (Obesity Program)
10/21/2023 8:00 AM Hans Pohl, M.D. Section on Urology Program: Day 2 Urology
10/21/2023 9:00 AM Anil Darbari, M.D., M.B.B.S., M.B.A. Constipation: Getting it to Work Out in the End Gastroenterology, Hepatology and Nutrition
10/21/2023 9:00 AM Kibileri Williams, M.B.B.S Appy Hour: a Current Update on Pediatric Appendicitis Surgery
10/21/2023 1:30 PM Olanrewaju (Lanre) Falusi, M.D. Educational Program and Annual Assembly for Medical Students, Residents, and Fellowship Trainees Pediatrician
10/21/2023 2:00 PM Brian Reilly, M.D. Noise 201 – More than Headphones! Otolaryngology
10/21/2023 2:00 PM Erin Teeple, M.D. Hernias, Hydroceles, and Undescended Testicles: When to Wait and When to Operate Surgeon
10/21/2023 3:30 PM Amanda Stewart, M.D. Section on Emergency Medicine Program: Day 2 Emergency Medicine
10/21/2023 3:30 PM Shideh Majidi, M.D., M.S.C.S. Healthcare Disparities in Management of Type 1 Diabetes and Diabetes Technology Endocrinology
10/21/2023 3:30 PM Natasha Shur, M.D. Genetic Testing Boot Camp Geneticist (RDI)
10/21/2023 5:00 PM Danielle Dooley, M.D., M.Phil Connecting School Systems and Health Systems: Successes and Opportunities Pediatrician
10/22/2023 8:00 AM Jaytoya Manget, DNP, FNP Pediatricians and School Attendance: Innovative Approaches to Prevent Chronic Absenteeism
10/22/2023 8:00 AM Simone Lawson, M.D. Section on Emergency Medicine Program: Day 3 Emergency Medicine
10/22/2023 8:00 AM Hans Pohl, M.D. Section on Urology Program: Day 3 Urology
10/22/2023 1:00 PM Lenore Jarvis, M.D., M.Ed. Section on Early Career Physicians Program
10/22/2023 5:00 PM Brian Reilly, M.D. Pediatric Hearing Loss: What’s New in Diagnostics, Prevention and Treatments Otolaryngology
10/23/2023 8:00 AM Rosemary Thomas-Mohtat, M.D. Point-of-Care Ultrasound Fundamentals Course Emergency Medicine
10/23/2023 9:00 AM Matthew Oetgen, M.D., M.B.A. Section on Radiology Program: Imaging Diagnosis and Management of Osteoarticular Infections Orthopaedic Surgery and Sports Medicine
10/23/2023 9:00 AM Christina Feng, M.D. Masses for the Masses: Abdominal Masses in Children Surgeon
10/23/2023 9:00 AM Narendra Shet, M.D. Section on Radiology Program: Imaging Diagnosis and Management of Osteoarticular Infections Radiology
10/23/2023 9:00 AM Shireen Atabaki, M.D., M.P.H. Section on Advances in Therapeutics and Technology Program Telemedicine
10/23/2023 1:00 PM Brian Reilly, M.D. Pediatric Otolaryngology: Back to Basics Otolaryngology
10/23/2023 1:00 PM Sonali Basu, M.D. Point-of-Care Ultrasound Critical Competency Course CCM
10/23/2023 1:00 PM Vanessa Madrigal, M.D. Joint Program: Section on Bioethics, Section on LGBT Health and Wellness and Section on Minority Health, Equity, and Inclusion Critical Care
10/23/2023 2:00 PM Rebecca Persky, M.D. Menstrual Disorders: Primary or Secondary Amenorrhea Endocrinology
10/23/2023 5:00 PM Christina Feng, M.D. Masses for the Masses: Abdominal Masses in Children Surgeon
10/24/2023 9:00 AM Vanessa Madrigal, M.D. Section Showcase: Applying Ethics Principles and Tools To Advocate for Vulnerable Populations Critical Care

 

little girl with cancer

A destination for pediatric oncology care: Children’s National Hospital’s T-cell therapy trials

When children are diagnosed with pediatric cancer, most doctors are forced to reach for the same standard therapies that were available decades ago. Research oncologists at Children’s National Hospital are changing that with clinical trials that will hopefully train the body’s immune system – specifically its T cells – to fight the tumors.

Holly Meany, M.D., and her colleague Amy Hont, M.D., oncologists and research scientists at the Center for Cancer and Immunology Research, have put together a pair of clinical trials that are investigating two pathways for using T cells to go after solid tumors.

“At Children’s National, we have a novel immunotherapy to offer to patients with relapsed or refractory solid tumors,” said Meany, director of the Solid Tumor Program. “This is a patient population who has failed standard therapy, so new technologies and treatments are always needed in this group.”

Where we started

Meany’s trial laid the foundation. She began the center’s research using a patient’s own blood sample to develop a targeted therapy and evaluate the safety and efficacy of this approach. In her study, scientists isolated the T cells, grew millions in a lab and reinfused them into the patient. The cells were replicated in an environment that was rich in three proteins that are commonly found on the surface of solid tumor cancer cells.

“Our hope and hypothesis are that when we give the T cells back to the patient, those T cells circulate and hunt down the cancer cells that have the tumor proteins,” Meany said. “We are hoping to use the patient’s own immune system to attack the cancer in an enduring way.”

Where we are headed

Hont’s phase 1 trial, which is currently recruiting participants, builds on Meany’s work using a healthy donor whose T cells have not been impacted by chemotherapy or other treatments. The cells can be prepared, stored and readily available for patients who need them. They are also matched through specific proteins on the patient’s own cells to bolster their effectiveness. The participants in this trial have Wilms tumors, rhabdomyosarcoma, neurosarcoma, soft tissue sarcoma or neuroblastoma, but conventional therapies including chemotherapy, radiation or surgery were unable to fully treat the disease.

In both studies, Hont said that the T cells have been given in an outpatient setting with fewer side effects compared to other cancer treatments aimed at high-risk malignancies.

“This allows patients to really maintain a good quality of life during a particularly hard time,” Hont said. “Also, these T cells are designed to act in the body the way that our immune system acts in a physiologic way. This means patients typically don’t have the severe side effects that we think of with chemotherapy or other therapies.”

Children’s National leads the way

The team at Children’s National is one of the few in the country to offer this kind of T-cell therapy for solid tumors. “Immunotherapy has been challenging for this patient population because the tumors are adept at finding out ways to evade treatment,” Hont said. “Giving patients a chance to receive a targeted T-cell therapy, while also maintaining a high quality of life, is something that’s special here.”

illustration of a nuclesome

Researchers publish first-ever atlas of cancerous mutations in histones

Leading genetic researchers at Children’s National Hospital have published the first pan-cancer atlas of key mutations that can drive molecular changes leading to tumors, creating a roadmap that could lead to new treatments for brain tumors and other cancers.

The research – published in npj Genomic Medicine – presents the first-of-its-kind atlas of histone mutations across pediatric, adolescent/young adult and adult cancers. The novel genetic work offers a framework allowing specific cancers to be redefined in the context of changes in histones, which are essential proteins that provide the structural support for chromosomes.

The big picture

“One of the major challenges that we face every day with pediatric, aggressive tumors, including pediatric high-grade gliomas, is that these tumors grow fast. Doctors often have to give patients 9 to 12 months from diagnosis,” said Javed Nazarian, Ph.D., scientific director of the Brain Tumor Institute at Children’s National and principal investigator at the Center for Genetic Medicine Research. “Children’s National has put together a team of clinicians that are truly devoted to finding a therapy for pediatric high-grade gliomas and aggressive pediatric brain tumors. Our dedicated team empowers translational research, from bench to bedside and reverse translation.”

In 2023, the American Cancer Society estimates that 9,910 children under age 15 will be diagnosed with cancer, making it the second leading cause of death among children. Because of treatment advances, 85% will survive, but many will be left with lifelong disabilities from their treatment. Nazarian and his team believe that identifying the underlying molecular alterations leading to cancers will be essential to finding new therapies that extend life expectancies and preserve quality of life.

The fine print

Histones are essential cellular structures, which prevent DNA from getting tangled. Nazarian and other researchers are investigating whether errors in histones could lead to cancers, including high-grade gliomas and other particularly sinister tumors that can strike young children. By mapping the mutations of the histone-encoding genes, Nazarian and his team believe they can find the drivers of tumors in many pediatric and adult cancers. In studying more than 12,000 tumors for the pan-cancer atlas, they cataloged patient ages, survival outcomes and tumor locations to reveal important trends among different cancers.

Overall, the team found that 11% of tumors had somatic histone mutations, with the highest rates observed among chondrosarcoma, a type of bone cancer (67%); pediatric high-grade glioma, a type of cancer that attacks glial cells in the brain and spinal cord (>60%); and lymphoma, a category of cancers in the lymph system (>30%).

“I think one implication of our study is that we are looking at the epigenomic changes of these mutations in a new light,” Nazarian said. “These mutations are not just specific to a particular tumor type, but they are indeed across a large spectrum of cancer types, and they come in different flavors that could potentially show a new avenue for treatments.”

newborn baby with bandaid on heel

JAMA Pediatrics editorial: A better approach for newborn screening

The medical community has an opportunity to update its approach to newborn screening (NBS) to be prepared for emerging technological advancements that will help diagnose children with rare diseases from their first weeks of life, according to an editorial from a leading Children’s National Hospital researcher published in JAMA Pediatrics.

“In health care, we are seeing ways in which we can identify more children who have rare diseases even earlier, in the newborn period, rather than waiting for children to develop symptoms or experience irreversible changes,” said Beth Tarini, M.D., M.S., M.B.A., associate director of the Center for Translational Research. “We have continued innovations in screening technology – with more on the way – that can be added to the screening programs overseen by all 50 states. Updating how we approach newborn screening presents an incredible opportunity for doctors and their patient-families.”

Why it matters

Newborn screening happens before the baby leaves the hospital, generally with a prick of the heel to take a small sample of blood to look for several dozen rare, debilitating disorders such as sickle cell disease, congenital hypothyroidism and cystic fibrosis. The current screening system has grown successfully for roughly 60 years and creates a network of state programs. Along the way, researchers have had extensive debates about which disorders to include, based on whether there are treatments and options for patients.

Dr. Tarini, a pediatrician who has done extensive research on NBS and related policies, said that the existing screening programs across all 50 states should be modernized, with federal research support and funding, to create a unified “learning newborn screening system” that derives information from the 4 million babies born each year and provides feedback to the medical community about best practices for babies who are diagnosed with a rare disease or at risk for developing one.

“A new approach will require resources and infrastructure, but as the technology advances, we should change our system to leverage the experience of doctors, patients, and NBS programs across the country,” Dr. Tarini said. “We have the will, the experience and the ability to transform the care for children with rare disease.”

Read the full editorial in JAMA Pediatrics.

photo of muscle collagen

New Becker muscular dystrophy drug on the horizon

photo of muscle collagen

Muscular dystrophies are a collection of genetic disorders that affect boys and cause progressive loss of muscle strength and disability throughout childhood. They impact the protein dystrophin, and other proteins associated with it, which helps strengthen muscles and protect them from injury.

A new corticosteroid – vamorolone – improves symptoms of Becker muscular dystrophy (BMD) with fewer side effects than the off-label treatments currently offered to patients, according to new research from Children’s National Hospital published in iScience.

Currently, there are no drugs approved to treat BMD, an inherited disorder that causes progressive muscle weakness. In preclinical models, daily treatment with vamorolone improved muscle strength and structure with results comparable to prednisolone, which is sometimes prescribed to patients with BMD. Unlike prednisolone, vamorolone is not known to stunt growth, weaken bone and cause negative behaviors.

“Patients with muscular dystrophy can fall anywhere on the spectrum from asymptomatic to facing life-threatening cardiac complications,” said Christopher Heier, Ph.D., principal investigator at the Center for Genetic Medicine Research at Children’s National. “We are excited to have our eye on a drug that may help manage the disease progression, without all the harmful side effects of the steroids currently being offered.”

The big picture

Muscular dystrophies are a collection of genetic disorders that affect boys and cause progressive loss of muscle strength and disability throughout childhood. They impact the protein dystrophin, and other proteins associated with it, which helps strengthen muscles and protect them from injury.

The FDA has approved four drugs to help mitigate the impact of Duchenne muscular dystrophy (DMD), the most severe and most common form of the disease, with dozens more drugs in the research pipeline for that disease subtype. In some cases, these drugs convert DMD into BMD, which is less severe but still greatly affects the quality of life. As a result, the number of patients living with BMD is growing, yet only two drugs are being studied to treat the Becker form of the disease.

Why we’re excited

The Food and Drug Administration is nearing approval for vamorolone to treat DMD. Researchers including Nikki McCormack, Ph.D., a postdoctoral fellow at Children’s National, found it has an added characteristic that makes it particularly helpful to BMD. “Excitingly, by reducing inflammatory signaling in the muscle, we find vamorolone can actually help to correct the underlying dystrophin protein deficiency in BMD through a newly discovered RNA-targeting mechanism.”

Investigators at Children’s National have been interested in expanding vamorolone’s possible use to BMD. Their work builds upon research finished late last year, when they created the first preclinical model to study drugs that could treat BMD. The model provides tremendous hope for those suffering from BMD around the world.

“By creating a pre-clinical model to test possible treatments, we are creating hope for boys living with this life-changing disorder,” said Alyson Fiorillo, Ph.D., principal investigator at the Center for Genetic Medicine Research at Children’s National. “This model, and the drugs it will lead to, will revolutionize how we treat those children living with this disorder.”

two balls -- one with a sad face and one with a happy face

Understanding quality of life for children with hypochondroplasia

two balls -- one with a sad face and one with a happy face

Children with hypochondroplasia have low parent-reported quality of life (QOL) scores, according to findings from researchers at Children’s National Hospital.

Children with hypochondroplasia have low parent-reported quality of life (QOL) scores, according to findings from researchers at Children’s National Hospital. The data, presented as part of a poster presentation at the Pediatric Endocrine Society (PES) annual meeting, also found older age and shorter height may further exacerbate effects on QOL.

Hypochondroplasia is a skeletal dysplasia that has an estimated prevalence of 1 in 15,000-40,000 births and is characterized by short stature and disproportionately short arms, legs, hands and feet.

Participants of the study were 13 prepubertal boys ages 3-11 and 13 prepubertal girls ages 3-10, all with height z-scores < -2.25 SD and genetically proven hypochondroplasia.

Moving the field forward

Effective medications for growth in patients with hypochondroplasia are limited. Children’s National is participating in an ongoing study of a new drug, vosoritide, used to treat children in this population and will compare pre- and post-intervention QOL scores.

How will this work benefit patients?

Understanding QOL of children with hypochondroplasia will help clinicians provide better care and support.

“Knowing how a medication affects QOL will help guide counseling about use of this medication,” says Nicole Rangos, M.D., pediatric resident at Children’s National and lead author of the study.

Dr. Rangos received the Human Growth Foundation Award for best growth-related abstract at the PES annual meeting in May 2023. The award was established in 2007 to encourage fellows training in pediatric endocrinology to pursue clinical and bench investigations that may lead to a better understanding of human growth.

 

Attendees at the inaugural symposium on AI in Pediatric Health and Rare Diseases

AI: The “single greatest tool” for improving access to pediatric healthcare

Attendees at the inaugural symposium on AI in Pediatric Health and Rare Diseases

The daylong event drew experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere to start building a community aimed at using data for the advancement of pediatric medicine.

The future of pediatric medicine holds the promise of artificial intelligence (AI) that can help diagnose rare diseases, provide roadmaps for safer surgeries, tap into predictive technologies to guide individual treatment plans and shrink the distance between patients in rural areas and specialty care providers.

These and dozens of other innovations were contemplated as scientists came together at the inaugural symposium on AI in Pediatric Health and Rare Diseases, hosted by Children’s National Hospital and the Fralin Biomedical Research Institute at Virginia Tech. The daylong event drew experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere to start building a community aimed at using data for the advancement of pediatric medicine.

“AI is the single greatest tool for improving equity and access to health care,” said symposium host Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator at the Sheikh Zayed Institute for Pediatric Surgical Innovation. “As a population, kids are vastly underrepresented in scientific research and resulting treatments, but pediatric specialties can use AI to provide medical care to kids more efficiently, more quickly and more effectively.”

What they’re saying

Scientists shared their progress in building digital twins to predict surgical outcomes, enhancing visualization to increase the precision of delicate interventions, establishing data command centers to anticipate risks for fragile patients and more. Over two dozen speakers shared their vision for the future of medicine, augmented by the power of AI:

  • Keynote speaker Subha Madhavan, Ph.D., vice president and head of AI and machine learning at Pfizer, discussed various use cases and the potential to bring drugs to market faster using real-world evidence and AI. She saw promise for pediatrics. “This is probably the most engaging mission: children’s health and rare diseases,” she said. “It’s hard to find another mission that’s as compelling.”
  • Brandon J. Nelson, Ph.D., staff fellow in the Division of Imaging, Diagnostics and Software Reliability at the Food and Drug Administration, shared ways AI will improve diagnostic imaging and reduce radiation exposure to patients, using more advanced image reconstruction and denoising techniques. “That is really our key take-home message,” he said. “We can get what … appear as higher dose images, but with less dose.”
  • Daniel Donoho, M.D., a neurosurgeon at Children’s National, introduced the audience to the potential of “Smart ORs”: operating rooms where systems can ingest surgery video and provide feedback and skill assessments. “We have to transform the art of surgery into a measurable and improvable scientific practice,” he said.
  • Debra Regier, M.D., chief of Genetics and Metabolism at Children’s National, discussed how AI could be used to diagnose and treat rare diseases by conducting deep dives into genetics and studying dysmorphisms in patients’ faces. Already, Children’s National has designed an app – mGene – that measures facial features and provides a risk score to help anyone in general practice determine if a child has a genetic condition. “The untrained eye can stay the untrained eye, and the family can continue to have faith in their provider,” she said.

What’s next

Linguraru and others stressed the need to design AI for kids, rather than borrow it from adults, to ensure medicine meets their unique needs. He noted that scientists will need to solve challenges, such as the lack of data inherent in rare pediatric disorders and the simple fact that children grow. “Children are not mini-adults,” Linguraru said. “There are big changes in a child’s life.”

The landscape will require thoughtfulness. Naren Ramakrishnan, Ph.D., director of the Sanghani Center for Artificial Intelligence & Analytics at Virginia Tech and symposium co-host, said that scientists are heading into an era with a new incarnation of public-private partnerships, but many questions remain about how data will be shared and organizations will connect. “It is not going to be business as usual, but what is this new business?” he asked.

DNA molecule

New genetic cause of overgrowth syndrome caused by SPIN4 variant

DNA molecule

A researcher at Children’s National Hospital identified a new genetic cause of overgrowth syndrome in Spindlin Family Member 4 (SPIN4), an epigenetic reader, in which a loss-of-function variant in SPIN4 causes a prenatal onset of extreme tall stature in a male individual, inherited in an X-linked semi-dominant fashion.

Overgrowth syndrome is a rare genetic childhood disorder commonly caused by pathogenic genetic variants in epigenetic writers, such as DNA or histone methyltransferases. A researcher at Children’s National Hospital identified a new genetic cause of overgrowth syndrome in Spindlin Family Member 4 (SPIN4), an epigenetic reader, in which a loss-of-function variant in SPIN4 causes a prenatal onset of extreme tall stature in a male individual, inherited in an X-linked semi-dominant fashion.

The study, published in JCI Insight, reported Spin4 knockout pre-clinical models recapitulating human phenotype and found evidence that SPIN4 normally binds specific modified histone peptides, promotes canonical WNT signaling and inhibits cell proliferation in vitro and that the identified frameshift variant lost all of these functions.

How does this work move the field forward?

“These findings prove that SPIN4 negatively regulates mammalian body growth, and loss of SPIN4 causes an overgrowth syndrome in humans and pre-clinical models, expanding our knowledge of the epigenetic regulation of human growth and development,” says Youn Hee Jee, M.D., endocrinologist at Children’s National and co-senior author of the study.

What did you find that excites you?

SPIN4 is the first epigenetic reader gene identified to cause overgrowth syndrome in humans.

“Understanding the full characteristics of the phenotype caused by SPIN4 variants will greatly advance our knowledge in epigenetic regulation of childhood growth and SPIN4-associated disorders,” Dr. Jee says.

How is Children’s National leading in this space?

Dr. Jee is leading a follow-up translational study to dissect the precise underlying pathobiology of overgrowth syndrome due to SPIN4 mutations. Using the knowledge, the ultimate goal of her work is to develop novel interventional approaches to treat childhood growth disorders.

U.S. News Badges

Children’s National Hospital ranked #5 in the nation on U.S. News & World Report’s Best Children’s Hospitals Honor Roll

U.S. News BadgesChildren’s National Hospital in Washington, D.C., was ranked #5 in the nation on the U.S. News & World Report 2023-24 Best Children’s Hospitals annual rankings. This marks the seventh straight year Children’s National has made the Honor Roll list. The Honor Roll is a distinction awarded to only 10 children’s hospitals nationwide.

For the thirteenth straight year, Children’s National also ranked in all 10 specialty services, with eight specialties ranked in the top 10 nationally. In addition, the hospital was ranked best in the Mid-Atlantic for neonatology, cancer, neurology and neurosurgery.

“Even from a team that is now a fixture on the list of the very best children’s hospitals in the nation, these results are phenomenal,” said Kurt Newman, M.D., president and chief executive officer of Children’s National. “It takes a ton of dedication and sacrifice to provide the best care anywhere and I could not be prouder of the team. Their commitment to excellence is in their DNA and will continue long after I retire as CEO later this month.”

“Congratulations to the entire Children’s National team on these truly incredible results. They leave me further humbled by the opportunity to lead this exceptional organization and contribute to its continued success,” said Michelle Riley-Brown, MHA, FACHE, who becomes the new president and CEO of Children’s National on July 1. “I am deeply committed to fostering a culture of collaboration, empowering our talented teams and charting a bold path forward to provide best in class pediatric care. Our focus will always remain on the kids.”

“I am incredibly proud of Kurt and the entire team. These rankings help families know that when they come to Children’s National, they’re receiving the best care available in the country,” said Horacio Rozanski, chair of the board of directors of Children’s National. “I’m confident that the organization’s next leader, Michelle Riley-Brown, will continue to ensure Children’s National is always a destination for excellent care.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals and recognizes the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News.

“For 17 years, U.S. News has provided information to help parents of sick children and their doctors find the best children’s hospital to treat their illness or condition,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “Children’s hospitals that are on the Honor Roll transcend in providing exceptional specialized care.”

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

The eight Children’s National specialty services that U.S. News ranked in the top 10 nationally are:

The other two specialties ranked among the top 50 were cardiology and heart surgery, and urology.

Germ cell tumor of testicle under microscopy

New research: Genes that drive testicular cancer identified

In the largest sequencing study to date on testicular cancer, researchers at Children’s National Hospital have identified genes that contribute to testicular germ cell tumors (TGCT), the most common cancer among young, white men.

The findings, published in European Urology, provide direction for future screening and treatment of this disease, which can strike during the teen years and often runs in families. While treatable when identified early, testicular cancer leads to infertility, mental health issues and sometimes death, making its identification crucial for young adults.

“Testicular cancer is really a young person’s disease,” said Louisa Pyle, M.D., Ph.D. , a pediatrician, medical geneticist and research geneticist at the Children’s National Rare Disease Institute. “Most folks who have testicular cancer are between the ages of 15 and 45. Even though testicular cancer is relatively rare in the cancer world, it results in the greatest number of years lost among all adult cancers.”

What we hope to discover

Dr. Pyle led a research team that included experts at the National Cancer Institute and the University of Pennsylvania to study families with multiple members diagnosed with testicular cancer. They used whole exome sequencing to identify variants in many genes that predisposed patients to TGCT. Their work suggests that multiple variants – inherited together – increased the risk for the disease and provides potential routes for drugs that could be used for prevention and treatment.

“We found many genes that help us understand how testicular cancer happens,” Dr. Pyle said. “Our hope is that we can use that to try to come up with better treatments or better ways to preserve fertility for people with testicular cancer or gonadal differences.”

The patient benefit

Testicular cancer most often strikes men of European ancestry. It is also more common among intersex patients and those with differences in sex development, which is a clinical and research focus for Dr. Pyle. Medically, these are children who have a change in the biological characteristics of sex, including their chromosomes, hormones, gonads or physical body parts.

By studying a more common version of testicular cancer, the team learned about the underlying genetics in a way that will benefit intersex patients.

“One of the things we do in medicine is study a common version of the rare thing,” Dr. Pyle said.  “Through this research, we learned that the same genes that cause intersex traits in some patients are also changed in subtle ways for people with testicular cancer. This is a way to study something that could improve care for those kids, by studying a group that has greater numbers.”

Children’s National Research & Innovation Campus

Research campus joins Global Network of Innovation Districts

Children’s National Research & Innovation Campus

At the RIC’s 12-acre campus in Northwest Washington, D.C., experts from Children’s National work alongside public and private partners in industry, universities, federal agencies, start-up companies and academic medical centers to find solutions to some of science’s most vexing challenges.

The Children’s National Research & Innovation Campus (RIC) has become the first science ecosystem dedicated to pediatric health to join a network of over three dozen innovation districts worldwide that integrate research space with sustainable communities to create models for urban work and living.

Known as the Global Network of Innovation Districts (GNID), the community was conceived to unlock the design of campuses like the RIC to create collaborations among highly trained professionals. At the RIC’s 12-acre campus in Northwest Washington, D.C., experts from Children’s National work alongside public and private partners in industry, universities, federal agencies, start-up companies and academic medical centers to find solutions to some of science’s most vexing challenges. The campus is surrounded by mass transit, open spaces, retail and housing, and it’s built on deep historic roots in the city as the former home of the Walter Reed Army Medical Center.

Kerstin Hildebrandt, vice president of research administration at the Children’s National Research Institute, said the team at the Research & Innovation Campus is excited to maximize its potential by joining this global network of economic drivers that are enhancing their communities and cities.

“We look forward to sharing our best practices, and we want to learn about how our national and international colleagues are tackling complex issues,” she said. “For example, we can learn how others are leveraging their assets to improve their communities and their response to health crises, climate change and other significant challenges.”

The GNID was launched in March of last year by The Global Institute on Innovation Districts (GIID), an international nonprofit focused on the advancement of innovation districts. With an initial group of 23 districts. GIID is now expanding the network to include approximately 20 additional districts that extend across Europe, North America, Latin America, Australia and Asia.

GIID’s Founder Julie Wagner said innovation districts have become a worldwide phenomenon. She said their leaders are recognizing that working and collaborating with their peers — from Melbourne to Medellin — is a powerful strategy to help these complex geographies leverage their assets in new ways.

“We are finding that innovation districts are willing to execute impactful strategies after holding highly curated exchanges with their peers,” Wagner said. “These are the places armed to solve some of the world’s most vexing challenges. From where I sit, we all need to give them as many tools as possible to help them get there.”

RNA molecule

New deep learning system helps scientists edit RNA

RNA molecule

The Children’s National team built DeepCas13 on a newer and less studied CRISPR platform, called CRISPR-Cas13d, which instead focuses on RNA.

Children’s National Hospital scientists have created a revolutionary machine-learning system that predicts the effects of changing ribonucleic acid (RNA) molecules using a gene-editing tool built on CRISPR technology.

Called DeepCas13, the system is among the world’s first deep-learning frameworks to recognize the challenges of editing RNA – and then applying data science and machine learning to solve the intricate problems that stem from modifying biological code. Details of the DeepCas13 system were published recently in Nature Communications.

Born from an international collaboration, DeepCas13 could provide the backbone for treatments for diseases based on errors in RNA, including debilitating neurodegenerative diseases such as Huntington’s disease and muscular dystrophy.

“I am an optimistic person, so I expect to have treatments within five to 10 years,” said Wei Li, Ph.D., principal investigator at the Center for Genetic Medicine Research at Children’s National. “Of course, there are going to be lots of obstacles. If we have a very good system, like DeepCas13, with very good performance that can generate treatments, the next problem is how we deliver the system to the right tissue in the patients.”

The big picture

Most research in this space has focused on a version of CRISPR – or Clustered Regularly Interspaced Short Palindromic Repeats – that edits DNA, called CRISPR-Cas9. The Children’s National team built DeepCas13 on a newer and less studied CRISPR platform, called CRISPR-Cas13d, which instead focuses on RNA. In doing so, researchers are opening the door to treating a host of disorders of RNA, given its biological role in coding, decoding, regulating and supporting gene expression.

DeepCas13 combines hundreds of thousands of data points with considerable computing power to help scientists target errant pieces of RNA, while minimizing any off-target changes that could damage the health of cells.

“We only want to target the RNA molecule that is causing diseases, and we don’t want the system to edit normal RNA,” said Xiaolong Cheng, Ph.D., a member of the Li lab and the first author of the study. “With DeepCas13, we can design highly efficient, and highly specific, rules.”

What’s ahead

The FDA has approved one method for delivering RNA treatments to cells, using a virus known as AAV or adeno-associated virus. So far, the gene therapy method has had limited applications. But Li and other researchers see the potential for life-changing treatments in the coming years, built on DeepCas13 and other advances.

The system was developed with partners from around the world, including the University of Illinois Urbana-Champaign and Northeastern University in Shenyang, China. It is open source and available for free to researchers looking for targets to treat RNA-related diseases.

Li says this international partnership is leading the way: “We tested our DeepCas13 model over other methods, and we confirmed that our method has the highest prediction accuracy.”

DeepCas13 was funded by grants from NIH and the Children’s National Research Institute.

illustration of cancer cell with target on it

Cancer Genetics Program growth: Q&A with Joyce Turner, M.S., C.G.C.

illustration of cancer cell with target on it

The Children’s National Cancer Genetics Program has witnessed a 57% increase in total number of patients seen in the past 4 years.

The Children’s National Cancer Genetics Program, established to identify individuals with a greater likelihood for certain types of cancer and provide early detection and treatment, has seen immense growth in the past few years. Joyce Turner, M.S., C.G.C., director of the Cancer Genetics Program, shares insights on the program and her vision for what’s next.

Q: How would you describe the recent growth of the program?

A: We’re extremely proud of the growth in the Cancer Genetics Program! Our program has witnessed a 57% increase in terms of the total number of patients seen (both new patients and patients seen for follow-up) in the past 4 years. A portion of this growth may be related to the COVID-19 pandemic as we were able to continue seeing patients in the comfort of their home. Our team has also expanded with the addition of a nurse coordinator in 2022.

Q: How does the work in this program benefit patients?

A: If we’re able to find a change, also known as a mutation, in a gene that explains a patient’s cancer diagnosis, we can support the care team with a better plan for how to screen the child moving forward. Since different genes can put patients at risk for specific types of cancers, knowing which gene mutation is present allows us to put a certain set of screening guidelines in place for long-term medical management.

Our goal with regular surveillance is to identify a tumor prior to becoming symptomatic when treatment is optimal for the patient and suffering is minimized. If we can identify a gene mutation in a patient, we can also test family members for the known gene change, so that they can benefit from screening as well if need be. After all, gene mutations can run in families. This also allows our team to share information with the patient’s family about the chance of recurrence in another child.

Q: What are you looking forward to in the future regarding advancements in the field of cancer genetics?

A: I am most looking forward to the newer technologies that will become the standard of care in the future.

Right now, we predominantly look at the ‘coding’ portions of our DNA, which are known as the exons. We are just beginning to learn about what lies within the introns, the genetic information between our exons, and we are finding that these regions are more important than we originally thought. RNA sequencing allows us to take a closer look at the effects of genetic changes within the introns. Right now, this technology is available on a limited basis from certain labs and for only a fraction of genes, but I see this becoming part of standard genetic testing in the near future.

Additionally, paired germline/somatic tumor testing (which looks for changes in cancer genes with which one is born and alterations in cancer genes within a tumor) has primarily been available in recent years on a research basis. However, the benefit of this technology is becoming more appreciated as it begins to move into mainstream practice. We have had to prove its feasibility and show that this type of testing can be performed in a timely manner. In doing so, this technology allows us to potentially determine the cause of a cancer, how to personalize one’s chemotherapeutic treatment based on molecular changes in the tumor and what we need to consider for screening purposes long-term. This type of genetic testing allows us to optimize overall patient treatment from the start. It’s an exciting time to be working in this field!

illustration of a brain

Inducing strokes in newborns to treat hemimegalencephaly

“The number one thing people are perplexed by is how well these babies recover and how they can only live with half a brain,” said Tayyba Anwar, M.D., neonatal neurologist and co-director of the Hemimegalencephaly Program at Children’s National Hospital. “People think if a child has half a brain that’s damaged or dysplastic, how are they functioning? But babies are so resilient. It still amazes me.”

The big picture

Children’s National experts have pioneered a novel approach of inducing strokes to stop seizures and improve neurodevelopmental outcomes in newborns under three months old with hemimegalencephaly (HME).

The procedure, called an endovascular embolic hemispherectomy, can be safely used to provide definitive treatment of HME-related epilepsy in neonates and young infants, according to a study in the Journal of NeuroInterventional Surgery.

Prior to this approach, the standard treatment was an anatomic hemispherectomy — surgical removal of the affected half of the brain. But infants had to be at least three months old to undergo such a complex surgery. Delaying surgery meant the persistent seizures compromised the development of the healthy half of the brain.

What they’re saying

In this video, Dr. Anwar and Panagiotis Kratimenos, M.D., Ph.D., neonatologist and co-director of Research in Neonatology at Children’s National, discuss the critically important neonatal care provided to babies who undergo endovascular embolic hemispherectomy and how protocols have evolved with each case to make this less invasive approach a feasible early alternative to surgical hemispherectomy.

Drs. Anwar and Kratimenos are part of the multidisciplinary team of neonatal neurologists, neurointerventional radiologists, neonatologists and neurosurgeons performing endovascular hemispherectomies.

photo of muscle collagen

New model to treat Becker Muscular Dystrophy

Researchers at Children’s National Hospital have developed a pre-clinical model to test drugs and therapies for Becker Muscular Dystrophy (BMD), a debilitating neuromuscular disease that is growing in numbers and lacks treatment options.

Their work – recently published in the Journal of Cachexia, Sarcopenia and Muscle – provides scientists with a much-needed method to identify, develop and de-risk drugs for patients with BMD.

“The impact of having a model to test pharmaceutical options cannot be overstated,” said Alyson Fiorillo, Ph.D., principal investigator at the Center for Genetic Medicine Research at Children’s National. “We have patients coming up to us at conferences offering muscle biopsies – on the spot – because they are so excited and relieved that treatments can be investigated.”

Caused by mutations in a gene that produces a protein called dystrophin, Becker is part of a collection of disorders known as muscular dystrophies that cause a progressive loss of muscle strength and increasing disability, starting in childhood. The FDA has approved four drugs to help mitigate the impact of the most common and severe subtype, Duchenne Muscular Dystrophy (DMD). In some cases, these drugs convert the Duchenne form of the disease into Becker, which is less severe but still greatly affects quality of life.

As a result, the population of BMD patients is growing, but patients lack treatments for this incredibly impactful disorder. Currently, the FDA has not approved any drugs for BMD. Only two drugs are in clinical trials, compared to 30 trials underway for DMD.

To address this, Children’s National researchers used CRISPR gene editing to create the first preclinical model of X-linked BMD, called the bmx model. This novel advancement will help researchers better understand BMD and eventually create the first drugs for BMD patients.

“Patients with Becker need therapeutic treatments, and we are excited to start working with the model to someday provide options,” said Christopher Heier, Ph.D., principal investigator at the Center for Genetic Medicine Research and co-author of the study. “Most patients with Becker eventually develop cardiomyopathy, and roughly half die from it. This model is the first step on a path to change that and other heartbreaking outcomes from this genetic disorder.”


blood cells

Half-matched cells – not identical – can help patients live longer, study finds

blood cells

Severe aplastic anemia (SAA) is a rare but serious blood disorder. Children and adults with SAA get very sick with low blood counts, infections or bleeding.

A new study, published in The Lancet Haematology, finds that patients of all races and ethnicities can get successful transplants for severe aplastic anemia (SAA) through haploidentical, or half-matched, bone marrow transplantation (BMT).

The big picture

SAA is a rare but serious blood disorder. Children and adults with SAA get very sick with low blood counts, infections or bleeding.

Relapsed SAA is a marrow failure disorder with high morbidity and mortality. Although this is often treated with BMT at relapse post-immunosuppressive therapy, historically under-represented minorities often struggle finding a suitably matched donor.

“If SAA does not respond to the first choice of therapy or comes back after a period of health, then we call this relapsed and refractory SAA,” says Blachy J. Dávila Saldaña, M.D., Blood and Marrow Transplant Specialist at Children’s National Hospital and corresponding author of the study. “BMT is the only cure for relapsed and refractory SAA.”

Moving the field forward

Many diagnosed patients do not have a fully matched donor to have a successful BMT. However, the study’s findings show that a haploidentical BMT from a family member can help people live longer.

“This especially helps people who are American Indian or Alaska native, Asian, Black or African American, Native Hawaiian, other Pacific Islander, more than one race or Hispanic,” Dr. Dávila adds. “It’s easier for people in these communities to find a related half-matched than a fully matched unrelated BMT donor.”

The patient benefit

Haploidentical BMT will greatly expand the ability of experts to safely treat patients of non-Caucasian ancestry that suffer from this condition.

“The half-matched transplant is becoming more standard and as safe as those with a fully matched donor,” Dr. Dávila says.

Children’s National was one of a handful of pediatric hospitals in the United States to participate in this open trial. Our experts will now provide the framework to expand these services to pediatric patients across the world.

Abstract Happy 2022 New Year greeting card with light bulb

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)