Cancer

2024 with a lightbulb instead of a zero

The best of 2024 from Innovation District

2024 with a lightbulb instead of a zero2024 marked another groundbreaking year for Children’s National Hospital, showcasing remarkable advances across the spectrum of pediatric medicine, research and healthcare innovation. From pioneering surgical procedures to breakthrough artificial intelligence applications, the institution continued to push the boundaries of what’s possible in children’s healthcare. Read on for our list of the most popular articles we published on Innovation District in 2024.

1. Prenatal COVID exposure associated with changes in newborn brain

A study led by researchers at Children’s National Hospital showed that babies born during the COVID-19 pandemic have differences in the size of certain structures in the brain, compared to infants born before the pandemic. The findings suggest that exposure to the coronavirus and being pregnant during the pandemic could play a role in shaping infant brain development.
(3 min. read)

2. Children’s National Hospital again ranked among the best in the nation by U.S. News & World Report

Children’s National Hospital was ranked as a top hospital in the nation by the U.S. News & World Report 2024-25 Best Children’s Hospitals annual rankings. This marks the eighth 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.
(2 min. read)

3. Children’s National performs first ever HIFU procedure on patient with cerebral palsy

In January 2023, a team of multidisciplinary doctors performed the first case in the world of using bilateral high intensity focused ultrasound (HIFU) pallidotomy on Jesus, a 22-year-old patient with dyskinetic cerebral palsy. The procedure is part of a clinical trial led by Chima Oluigbo, M.D., pediatric neurosurgeon at Children’s National Hospital.
(3 min. read)

4. Novel ultrasound device gets FDA breakthrough designation with Children’s National support

A novel ultrasound device developed by Bloom Standard received the Food and Drug Administration’s valued breakthrough device designation with the help of Children’s National Hospital. The device that enables autonomous, hands-free ultrasound scans to be performed anywhere, by any user.
(2 min. read)

5. First-of-its-kind pilot study on the impacts of Lyme disease in pregnancy and infant development

Understanding the effects of Lyme disease on the developing fetal brain is essential to ensure timely prenatal and postnatal treatments to protect the fetus and newborn. In response to this need, Children’s National Hospital is leading a pilot study to establish the groundwork needed for a larger study to determine the effect of in utero exposure to Lyme disease on pregnancy and early childhood neurodevelopmental outcomes.
(3 min. read)

6. Earliest hybrid HLHS heart surgery kids thrive 5 years later

Five years ago, Cayden was born 6 weeks early weighing less than four pounds and at risk of dying from her critical congenital heart disease. Today, she’s a happy five-year-old. Early diagnosis of her hypoplastic right ventricle, double inlet left ventricle and critical coarctation of the aorta allowed for the team at Children’s National Hospital to create a careful plan for safe delivery and to offer an innovative hybrid HLHS surgical approach at the hospital within 24 hours after she was born.
(1 min. read)

7. Wayne J. Franklin, M.D., F.A.C.C., named senior vice president of the Children’s National Heart Center

Children’s National Hospital appointed Wayne J. Franklin, M.D., F.A.C.C., as the new senior vice president (SVP) of the Children’s National Heart Center. In this role, Dr. Franklin oversees the full spectrum of heart care services including cardiac imaging and diagnostics, interventional cardiology, electrophysiology, cardiac anesthesia, cardiac surgery and cardiac intensive care.
(2 min. read)

8. Artificial – and accelerated – intelligence: endless applications to expand health equity

By pioneering artificial intelligence (AI) innovation programs at Children’s National Hospital, Marius George Linguraru, D.Phil., M.A., M.Sc., and the AI experts he leads are ensuring patients and families benefit from a coming wave of technological advances. The team is teaching AI to interpret complex data that could otherwise overwhelm clinicians.
(4 min. read)

9. Evidence review: Maternal mental conditions drive climbing death rate in U.S.

Painting a sobering picture, a research team led by Children’s National Hospital culled years of data demonstrating that maternal mental illness is an under-recognized contributor to the death of new mothers. They called for urgent action to address this public health crisis.
(3 min. read)

10. Nathan Kuppermann, M.D., M.P.H., named chief academic officer and chair of Pediatrics

Children’s National Hospital appointed Nathan Kuppermann, M.D., M.P.H., as its new executive vice president, chief academic officer and chair of Pediatrics. In this role, Dr. Kuppermann oversees research, education and innovation for the Children’s National Research Institute as well as academic and administrative leadership in the Department of Pediatrics at George Washington University School of Medicine & Health Services.
(2 min. read)

11. First global clinical trial achieves promising results for hypochondroplasia

Researchers from Children’s National Hospital presented findings from the first clinical trial of the medication vosoritide for children with hypochondroplasia – a rare genetic growth disorder. During the phase 2 trial, researchers found vosoritide increased the growth rate in children with hypochondroplasia, allowing them to grow on average an extra 1.8 cm per year.
(2 min. read)

12. Pioneering research center aims to revolutionize prenatal and neonatal health

Since its establishment in July 2023, the Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital has gained recognition through high-impact scientific publications, featuring noteworthy studies exploring the early phases of human development.
(3 min. read)

Kids sitting at desks in school

Radon in school: A hidden worry for eastern Pennsylvania students

Kids sitting at desks in school

Some students may be exposed to nearly twice the annual dose of natural background radiation, estimated by the U.S. Nuclear Regulatory Commission at 3.1 mSv (310 mrem).

A Children’s National Hospital researcher teamed up with a high school student from Bethlehem, Pa., to shed light on radon, a silent health risk that may be present in some schools.

They examined radon levels in five eastern Pennsylvania school districts. The neighborhoods surrounding all 37 public schools had average radon levels exceeding the federal action level, or 4.0 pCi/L. According to their findings, the same could be true of the school buildings.

In a new research letter published in JAMA Network Open, researchers found some students may be exposed to nearly twice the annual dose of natural background radiation, estimated by the U.S. Nuclear Regulatory Commission at 3.1 mSv (310 mrem).

An odorless and invisible gas, radon is the leading cause of lung cancer among nonsmokers and the second overall cause of lung cancer nationwide. Its greatest danger lies in prolonged exposure, a risk amplified in school settings where children and teachers spend extensive hours. The U.S. Environmental Protection Agency (EPA) estimates more than 70,000 classrooms have high short-term radon levels.

“This study highlights the urgent need for radon testing in schools,” said Beth Tarini, M.D., M.S., M.B.A., co-director of the Center for Translational Research at Children’s National and the manuscript’s senior author. “Unchecked exposure to radon in these settings could have significant short- and long-term health effects, particularly for children.”

The EPA has found that approximately 20% of schools nationwide have done some testing, and only . In the Washington, D.C., region, Dr. Tarini says testing is often done:

  • The District of Columbia requires public schools to test for radon and publicize the results. If the results are above the federal limit of >4pCi/L, the schools are required to mitigate the risk.
  • Maryland doesn’t require schools to test for radon, but some schools test. The state’s largest school district — Montgomery County Public Schools — has been testing for radon since the late 1980s and retests facilities every five years.
  • In Virginia, the commonwealth requires public schools to test for radon, make the results public and report the results to the state.

Brian Yang, the study’s first author, called for action in Pennsylvania and regions with known radon risks.

“This research underscores the need to test radon levels in schools and, if necessary, mitigate,” said Yang, a senior at Moravian Academy in Bethlehem, Pa. “Addressing this invisible and under-recognized threat should be a public health priority.”

For more details, read the full study — “Estimated Radon Exposure in Eastern Pennsylvania Schools” — in JAMA Network Open.

 

 

Attendees at the 2nd annual Cell & Gene Therapy Symposium

Regional powerhouse: Cell and Gene therapy leaders from mid-Atlantic forge connections

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Nearly 200 biomedical leaders from Washington, D.C., Maryland, and Virginia gathered at the Children’s National Research & Innovation Campus for the 2nd annual Cell & Gene Therapy Symposium. The event showcased groundbreaking developments in rare disease treatments and underscored the importance of regional collaboration.

“By targeting diseases at the cellular level, we are on the cusp of breakthroughs in cell and gene therapy that will transform medicine,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research (CCIR) at Children’s National Hospital and a host of the symposium. “Progress will accelerate if we build partnerships beyond our own organizations.”

The big picture

Scientists and clinicians have worked for more than two decades to develop cell and gene therapies aimed at treating diseases on a cellular level. The past few years have been particularly promising as investment in science has led to advancements. Children’s National is at the forefront, as one of the first pediatric hospitals in the world to offer commercial gene therapies for sickle cell disease.

Many more treatments for rare diseases are in development at Children’s National and beyond. Leaders at CCIR are actively building collaborations with companies, academic institutions and enterprises across the mid-Atlantic region to accelerate these efforts.

During the symposium, Eugene Hwang, M.D., chief of Oncology at Children’s National, addressed the urgent need for more effective and less toxic treatments for pediatric brain tumors. He highlighted the potential of combining immunotherapies with innovations like low-intensity focused ultrasound, which can open the blood-brain barrier temporarily to improve drug delivery to tumors.

“With collaboration between the lab and clinic, alongside industry partners and even between hospitals, we can finally make strides I haven’t seen in my entire career,” Dr. Hwang said. “It’s an incredibly inspiring time for all of us.”

Why it matters

Experts from organizations as diverse as MaxCyte, ScaleReady, RoosterBio, PSC Biotech, Qiagen, FujiFilm and the Frederick County Office of Economic Development came together for the daylong conversation.

Michael Friedlander, Ph.D., executive director of the Fralin Biomedical Research Institute at Virginia Tech, emphasized the critical role of regional partnerships in fulfilling the potential of these emerging therapies. He pointed to the collaborative research between Children’s National and Virginia Tech on brain tumors, where bioengineers and cancer researchers are working side-by-side to create new treatments.

“We are now able to begin delivering these leading-edge therapies to patients,” Dr. Friedlander said. “For example, those who live in rural settings often have much less access to such frontline medical innovations. By collaborating with Children’s National and gaining access to urban pediatric populations, as well as patients in our more rural area, we can start to bring these therapies to a much broader audience.”

What’s next

Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National, observed that other regions in the U.S. are uniting to advance scientific discoveries with the backing of government, academia and industry. He hopes to see similar collaboration across the D.C., Maryland, and Virginia area, known as the DMV. Children’s National is leading an initiative called CHARM – the Capital Health and Mid-Atlantic Regenerative Medicine – to bring regional experts together for webinars, networking events and partnership opportunities.

“There’s significant interest in cell and gene therapy worldwide,” said Dr. Hanley, a symposium host. “I see an even greater interest in creating cell and gene therapy hubs. The time is right for our mid-Atlantic region, and I’m excited to see what unfolds in the next five years.”

Drs. Wessel, Dome and Kim with Michelle Riley-Brown and the Speight’s

Honor bestowed on AeRang Kim, M.D., Ph.D.

Drs. Wessel, Dome and Kim with Michelle Riley-Brown and the Speight’s On November 1, Children’s National Hospital installed AeRang Kim, M.D., Ph.D., as the first holder of The Lexi Speight Chair in Pediatric Oncology.

Dr. Kim is clinical research director for the Oncology Division within the Cancer and Blood Disorders Center at Children’s National. She is a tenured professor of pediatrics at the George Washington University School of Medicine and Health Sciences.

The big picture

Dr. Kim joins a distinguished group of Children’s National physicians and scientists who hold an endowed chair. Children’s National is grateful to generous donors who altogether have funded 49 professorships.

Professorships support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s commitment to advancing and sustaining knowledge.

Why it matters

Since arriving at Children’s National in 2010, Dr. Kim has played a pivotal role in our solid tumor program. She leads the renowned multi-disciplinary Sarcoma Clinic, which includes a comprehensive team of oncologists, nurses, orthopedic surgeons, radiologists, a genetic counselor and a physical therapist. It is one of the few of its kind in the country. Dr. Kim’s dedication and leadership have been instrumental in earning Children’s National recognition as a Sarcoma Alliance Center of Excellence.

Dr. Kim leads clinical trials evaluating new pediatric solid tumor treatments across multiple institutions. She pioneers precision approaches using targeted drugs, advanced devices and cell therapies. Her innovative work attracts numerous grants, including a recent $1.3 million from the Department of Defense.

“The future of cancer treatment is in precision medicine,” says Dr. Kim. “As The Lexi Speight Chair of Pediatric Oncology, I will explore new ways to design clinical trials to accelerate development of new therapies for solid tumors. This could change the paradigm for pediatric cancer treatment.”

Moving the field forward

The Speight family, through their vision and generosity, are ensuring that Dr. Kim and future holders of this chair will launch bold, new initiatives to rapidly advance the field of pediatric oncology, elevate our leadership and improve the lifetimes of children with solid tumors.

“When Lexi died, we had a decision to make about how to channel our grief,” Cyndi Speight, Lexi’s mom, remembered. “And do what we could to help other children and families from experiencing what we did.” And so, Cyndi, her husband Petr, and their daughter Sam established The Lexi Speight Chair in Pediatric Oncology with support from community partners in loving memory of Lexi. The Speight family started Laps for Lexi, an annual 5K run/walk that raised money for both pediatric cancer at Children’s National and a scholarship at Sandy Spring Friends School. This successful event ran for 13 years, bringing hope to children and families. The Speight family’s dedication and passion for advancing solid tumor care ensures that Lexi’s legacy lives on in our pursuit of better treatments for children.

2024-25 US News Badges

Children’s National again ranked among the best in the nation by U.S. News & World Report

2024-25 US News BadgesChildren’s National Hospital in Washington, D.C., was ranked as a top hospital in the nation by the U.S. News & World Report 2024-25 Best Children’s Hospitals annual rankings. This marks the eighth 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.

This year, U.S. News ended ordinal rankings on its Honor Roll. Instead of assigning a numerical rank from 1 to 10, all hospitals on the Honor Roll will be recognized as having attained the highest standards of care in the nation.

In addition, Children’s National tied for #1 pediatric hospital in the Mid-Atlantic region, which includes New York, New Jersey, Delaware, Pennsylvania, the District of Columbia, West Virginia and Virginia. It’s also best in the Mid-Atlantic in Neonatology.

For the fourteenth straight year, Children’s National ranked in 10 specialty services. New this year, U.S. News included behavioral health as a service line in the rankings. Since it’s the first year, there are no ordinal rankings for behavioral health, but the Children’s National program was named one of the top 50 programs in the country.

“In my first year here, I witnessed what makes Children’s National so special — our commitment to collaboration, empowering one another, and charting a bold path forward for pediatric care,” said Michelle Riley-Brown, MHA, FACHE, president and chief executive officer of Children’s National. “I’m proud U.S. News again recognized Children’s National as one of the top in the nation and the highest-ranked pediatric hospital in D.C., Maryland and Virginia. Together, we’ll continue to push the boundaries of care, research and innovation to make a difference for those who matter most — the kids.”

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 nearly two decades, U.S. News has published Best Children’s Hospitals to empower the parents and caregivers of children with complex medical needs,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “Children’s hospitals appearing on the U.S. News Honor Roll have a track record of delivering unparalleled 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 Children’s National specialty services that U.S. News ranked in the top 10 nationally are:

The other four specialties ranked among the top 50 are Behavioral Health, Cardiology and Heart Surgery, Pulmonology and Lung Surgery, and Urology.

Dr. Andrew Campbell

Meet Dr. Andrew Campbell: Trailblazing treatment for patients with sickle cell disease

Andrew Campbell, M.D., remembers the first time he met a patient with sickle cell disease in the early years of his medical training. It was a brief interaction that had a profound effect on the trajectory of his career.

Sickle cell disease is an inherited blood disorder that primarily affects African American and Hispanic American children. The disease can cause severe pain events as well as progressive organ damage in patients.

This life-altering disease has affected children for more than a century, yet only one FDA-approved drug for treatment of sickle cell disease was developed in the first 100 years of its existence. Recognizing the health inequities that have contributed to an overall lack of therapies and providers in the field, Dr. Campbell knew he had to act.

“It was an area that needed a lot of resources, but also a lot of research and understanding of what our patients are going through. So, that was my initial launch into the field of Hematology and Oncology,” he explained, and he’s been an instrumental leader ever since.

For the past seven years, Dr. Campbell has served as the director of the Comprehensive Sickle Cell Disease Program at Children’s National Hospital — one of the largest sickle cell programs in the country, treating nearly 1,400 patients a year. Locally, he is Principal Investigator for the American Society of Hematology Sickle Cell Research Collaborative’s DMV Sickle Cell Consortium that includes several area sickle cell clinics including Northern Virginia, Richmond, Washington DC and Maryland.

In December 2023, the FDA approved two new gene therapies (CASGEVY™ and LYFGENIA™) to treat patients with sickle cell disease. Children’s National became one of the few pediatric hospitals in the country to offer these therapies, going on to then treat the first patient in the U.S. using the gene therapy method.

Dr. Campbell, who is treating the 12-year-old patient, says his team is excited about the future of these non-chemotherapy treatments and the curative possibilities they will bring to the field.

Despite being part of this significant milestone in the sickle cell community, Dr. Campbell says the work doesn’t stop there. His passion for making a difference and his impact on patients extends far beyond just Washington, D.C., and even the U.S.

For example, Dr. Campbell directs a research group called the Consortium for the Advancement of Sickle Cell Disease Research (CASiRe), with other sickle cell providers across the world. He says one of their goals is to better understand the ways that sickle cell can present itself in patients based on the country in which they receive treatment. “It’s really showing that based on the geographic difference of patients, it has implication in how they receive care,” he explains, adding that the group hopes to take what they learn in these studies to design more inclusive clinical trials in the future.

When he’s not devoting his time to research, you can find Dr. Campbell taking the fight for patients with sickle cell disease directly to lawmakers.

“I have gone to Capitol Hill a number of times to advocate for access and improvement of treatments for sickle cell disease,” he says, hoping that by using his voice and presenting his research, he can help the current generation, as well as the future generation of patients, get the care they deserve.

Screen shot of educational video

What’s a TAA-T? Advocates create videos to translate science for patients

As researchers develop groundbreaking cellular therapies to treat pediatric solid tumors, physicians are preparing new ways to explain how these treatments work to patients and caregivers.

In a series of educational videos, scientists from Children’s National Hospital and institutions worldwide are offering tutorials on these novel treatments and how they target solid tumors at the cellular level.

“Let’s start by breaking down what a tumor-associated antigen-specific T (TAA-T) cell is,” Children’s National Research Technician Sammy Murphy says in one new video. “Our aim is to harness the power of T cells to identify and attack cancer cells.”

In less than six minutes, Murphy provides a short course on the details of these TAA-T cells and how her team combines their expertise in biology, medicine, bioinformatics, quality assurance and more to create the new therapies. “This collaborative team spirit has been a huge motivating factor and represents the best of what science can be,” she explains.

The big picture

Children’s National summer student Diana Kentell, a senior at Pratt Institute of Art studying digital art and 2D animation, created this video and a collection of others for the Cancer Grand Challenges (CGC), sponsored by the National Cancer Institute and Cancer Research UK. In 2022, the CGC awarded $25 million to Children’s National, the University College of London Cancer Institute and its partners on the NexTGen team to develop new therapies for pediatric solid tumors using CAR T cells.

The NexTGen team includes six patient advocates who have all been touched by pediatric tumors and support the scientists by providing the patient perspective on research and new treatments. These videos are a slice of the group’s efforts.

C. Russell Y. Cruz, M.D., Ph.D., a translational immunologist on the NexTGen team who oversaw Kentell’s video project, says bridging the gap between scientists and their patients who enroll in clinical trials will be essential to ensuring patients weigh the possibilities and the risks.

“Patient advocates help us understand our work from their perspective, making our science accessible to everyone,” Dr. Cruz said. “Engaging with such dedicated individuals often helps us refine our own ideas and provides invaluable insights. Most importantly, they remind us of our ultimate goal: to free future generations from the burden of pediatric cancer.”

Why we’re excited

In addition to the video on TAA-T cells, the team has assembled a collection of videos on killing assays, tumor slice assays and CAR T-cell manufacturing, which will help patients learn about the treatments when the clinical trials start.  Sara Wakeling, who leads the NexTGen team’s patient advocates, said this toolkit will be a vital resource.

“Each of us came to this advocacy work because we were deeply affected by pediatric cancer.  We aim to ensure that the child’s voice is central to the research and that the science is communicated in an informative and digestible way for patients’ families and the public,” Wakeling said. “With these videos, lay summaries of manuscripts and other explainers, we will have concrete information to share with families as soon as the new CAR T-cell therapies are ready for clinical trials.”

A clean room at CNRI.

CellBuilder: A ready-made solution for cell & gene therapy manufacturing

A clean room at CNRI.

With CellBuilder and our global partnerships, Children’s National hopes to expand access to groundbreaking cell and gene therapy treatments as they take off in the next five years.

With cell and gene therapies poised to reshape cancer and rare disease treatments, researchers at Children’s National Hospital are pioneering ready-to-use solutions that will bring these cutting-edge therapies directly to hospitals and other treatment centers, shrinking the distance between doctors and patients.

“The next five years are going to be a period of tremendous growth for cell and gene therapy,” said Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National. “Currently, there’s no shortage of interest from the medical community, but there’s a shortage of people who can manufacture and administer this care. We’re looking for ways to get these treatments to the patients by providing other institutions the tools they need to launch these programs cost-effectively, safely and efficiently.”

Called CellBuilder, the starter kits for cell and gene therapy programs could transform the landscape for pediatric patients.

The big picture

Dr. Hanley and many members of the Children’s National team have been working in cell and gene therapy for more than a decade, gaining extensive experience in the technical and regulatory hurdles inherent in creating treatments that target diseases at their source.

In cell therapy, a specific cell type is modified and transferred to a patient with a payload that can target a disease or disorder. For example, T cells may be modified and delivered to patients to teach their immune systems to fight cancer.  In gene therapy, a patient’s genetic code is modified to treat or prevent diseases, such as sickle cell disease, cancers and other genetic disorders. This can be done by introducing a healthy copy of a gene, repairing a faulty gene or altering a gene’s function.

Children’s National has become a leader in manufacturing virus-specific T cells, one method of delivering cell therapies, and the Cellular Therapy Program has conducted consortium-led, multi-center trials. Many other healthcare sites across the country want to start programs offering this care at their facilities.

The holdup in the field

Starting a cell and gene therapy program from scratch can take years of effort, training and money. That’s why Jay Tanna, M.S., R.A.C., quality assurance manager of the Cellular Therapy Program at Children’s National, said the team is creating CellBuilder starter kits, which include the manufacturing protocol and the resources necessary to launch a cell therapy program almost instantly.

“With a suitable knowledge base, institutions can start their own cellular therapy program at the point of care, using our manufacturing protocols, vetted reagents and other key elements of the process,” Tanna said. “Of course, interested institutions would have to meet regulatory requirements and establish a clean room to manufacture these therapies. If they want to use CellBuilder to run a clinical trial, they can do that. If they want to take it to become a licensed product, they can do that, too.”

Children’s National has worked with more than five institutions to build their virus-specific T-cell program and is now using the kits to accelerate and commercialize the process to increase patient access. The lab has also entered into a memorandum of understanding with the Tokyo-based Hitachi Global Life Solutions, Inc., an innovative modular clean room manufacturer, with the goal of offering a bundled solution.

Why we’re excited

Dr. Hanley and his colleagues say that the partnerships Children’s National is forging as they consult with other experts in this field will expand access to cell and gene therapy across the country—and hopefully around the world.

“It used to be that, to get a CAR T cell, you would collect the cells at Children’s National, ship them to a company like Novartis, have the therapy manufactured there and then shipped back,” said Michael Keller, M.D., who co-led a first-of-its kind immunotherapy trial as the Translational Research Laboratory director at the Children’s National Cell Enhancement and Technologies for Immunotherapy Program. “It was expensive, time-consuming and limited patient access. Now, there’s growing interest in manufacturing at each site, just like you would with a bone marrow transplant.”

With CellBuilder and our global partnerships, Children’s National hopes to expand access to groundbreaking cell and gene therapy treatments as they take off in the next five years, extending lifetimes and improving the quality of life for children suffering from rare disorders.

“We’re trying to capture the momentum underway in the field by providing this kit so that institutions don’t have to know how to do everything,” Dr. Hanley said. “We provide all the knowledge, a reagent list and everything else they need—and they provide the care.”

Leaders from pediatric healthcare, federal organizations, academia, industry and patient advocacy groups gathered at the Children’s National Research & Innovation Campus.

Access4Kids: A new model to pay for pediatric cell and gene therapies

Science is pioneering cures for pediatric rare diseases in a coming wave of new cell and gene therapies. However, the biopharmaceutical industry’s insistence on large patient populations and high profit margins may prevent these life-saving treatments from reaching the children who desperately need them. When successful therapeutics fail to see commercialization, experts say they have fallen into the “Valley of Death.”

To address this, leaders from pediatric healthcare, federal organizations, academia, industry and patient advocacy groups gathered at the Children’s National Research & Innovation Campus. Their objective: build a new framework to deliver these transformative drugs to clinics worldwide.

Meet the team forming Access4Kids, a nonprofit whose mission is to build new pathways to pay for cures and provide hope to children with life-limiting diseases. This group is working to change medicine and how we pay for it, under the leadership of Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research, Crystal Mackall, M.D., director of the Stanford Center for Cancer Cell Therapy, Julie Park, M.D., Oncology Department chair at St. Jude Children’s Research Hospital, and Alan Wayne, M.D., pediatrician-in-chief at Children’s Hospital Los Angeles.

Cheng-Chia “Fred” Wu, M.D., Ph.D.

Expanding team innovates to take on pediatric brain tumors

Cheng-Chia “Fred” Wu, M.D., Ph.D.

Cheng-Chia “Fred” Wu, M.D., Ph.D., joins the team at the campus as an assistant professor at Virginia Tech’s Fralin Biomedical Research Institute. Image credit: Fralin Biomedical Research Institute.

Experience, talent and technology are coming together at the Children’s National Research & Innovation Campus to solve the complex challenges of treating pediatric brain tumors through a growing partnership between Children’s National Hospital and Virginia Tech.

Cheng-Chia “Fred” Wu, M.D., Ph.D., joins the team at the campus as an assistant professor at Virginia Tech’s Fralin Biomedical Research Institute. He hopes to improve treatment for pediatric brain tumors and other cancers by leveraging technological advances in focused ultrasound and studying how this modality can be combined with other novel therapies. Children’s National physicians and scientists are collaborating with Virginia Tech scientists to develop these new approaches.

Why we’re excited

Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research and interim chief academic officer at Children’s National, said collaborations — including the partnership between Children’s National and Virginia Tech — are essential to solving formidable scientific challenges.

“We are thrilled to be working with Dr. Wu to develop cutting-edge therapeutics for pediatric brain tumors,” Dr. Bollard said. “With Dr. Wu’s experience and the talents of our team at Children’s National, I have great hope that we will be able to combine our novel technologies and therapies to provide tremendous breakthroughs for treating pediatric patients with brain tumors.”

Before joining Virginia Tech, Dr. Wu was an assistant professor of radiation oncology at Columbia University Irving Medical Center in New York, where he treated pediatric cancers and central nervous system malignancies.

“Partnering with Children’s National connects us to a world-class clinical trial institute that has been a pioneer in treating brain tumors with focused ultrasound technology, and this presents a unique opportunity to help children and families struggling with cancer,” Dr. Wu said. “I can’t wait to see where this takes us.”

Dr. Wu played a key role in the Initiative for Drug Delivery Innovation for Childhood Brain Tumors at Columbia, developing a bench-to-bedside platform to facilitate the translation of promising technologies for targeted drug delivery in children with brain tumors.

Within three years, the team demonstrated the safety and feasibility of using focused ultrasound in the brainstem and adding radiation in preclinical models. They then opened two clinical trials for kids with relapsed diffuse midline glioma, an aggressive and difficult-to-treat brain tumor that occurs in the brain stem, thalamus and spinal cord.

What’s ahead

Dr. Wu will be involved in a wide range of research touching both organizations, including veterinary medicine and biomedical engineering at Virginia Tech.

Michael Friedlander, Ph.D., executive director of the Fralin Biomedical Research Institute at Virginia Tech Carilion and vice president for health sciences and technology at Virginia Tech, welcomed Dr. Wu’s experience as a pediatric radiation oncologist, translational physician-scientist and clinical trialist who has led an innovative drug delivery program.

“He is armed with a unique set of skills to identify promising new technology and implement it in areas of great need for treatment of pediatric cancers,” Dr. Friedlander said. “We are absolutely delighted to have Dr. Wu as part of the team.  He represents a powerful new part of the strong partnership between Virginia Tech and Children’s National Hospital for addressing pediatric brain cancer.”

Assessing psychosocial risk, patient readiness for sickle cell gene therapy

The CureSCi Patient Readiness and Resilience Working Group brought together behavioral health clinicians and scientists from across the U.S. with expertise in sickle cell disease to develop recommendations for assessing and promoting patient readiness for gene therapy.

Two gene therapies for sickle cell disease were recently approved by the U.S. Food and Drug Administration (FDA) and are now commercially available in the U.S. This marks a historic shift in the treatment of sickle cell disease (SCD) and represents a leap forward more broadly for the medical community, opening a range of exciting possibilities for the development of novel therapeutics for other diseases. However, these new therapies are not without medical and psychological risks; therefore, the Cure Sickle Cell Initiative (CureSCi) of the National Heart, Lung and Blood Institute (NHLBI) convened a Patient Readiness and Resilience Working Group to develop recommendations for the assessment of psychosocial readiness for gene therapy.

What’s been the hold-up in the field?

Clinicians have long recognized that psychological and social issues have the potential to affect treatment outcomes following disease-modifying or transformative treatments, such as hematopoietic stem cell transplants. The same concerns exist for gene therapies, but there has not been clear guidance about the best ways to evaluate patient readiness and psychosocial risk and resilience factors in these contexts.

How does this work move the field forward?

The CureSCi Patient Readiness and Resilience Working Group brought together behavioral health clinicians and scientists from across the U.S. with expertise in SCD, as well as caregivers and patients with the lived experience of having SCD, to develop recommendations for assessing and promoting patient readiness for gene therapy. The resulting consensus statement outlines clear and practical guidance for conducting pre-gene therapy patient readiness assessments.

“This is an exciting time for the sickle cell and medical communities,” says Steven Hardy, Ph.D., director of Behavioral Health Services in the Divisions of Hematology, Oncology and Blood and Marrow Transplantation at Children’s National Hospital and lead author on the consensus statement. “But it is also a time to exercise caution to ensure that, in the cloud of such enthusiasm, we do not lose sight of the complex ways that human psychology, relationships and biology interact to influence health.”

How will this work benefit patients?

This new guidance for evaluating psychosocial readiness will ensure that important issues — such as the degree to which patients have been informed of and understand key treatment details, are interested in and motivated to pursue treatment, and have considered how undergoing gene therapy will affect their activities, relationships and mental health — are considered and patients are provided the necessary supports.

“These recommendations offer a blueprint and a charge to institutions, payors and policymakers around the world to prioritize the psychosocial well-being of patients with SCD undergoing gene therapy,” says Dr. Hardy.

How is Children’s National leading in this space?

Children’s National has participated in gene therapy clinical trials and is the first institution globally to treat a patient with SCD with one of the new commercially available gene therapies. Dr. Hardy chaired the CureSCi Patient Readiness and Resilience Working Group that developed the consensus recommendations. Psychologists in the Divisions of Hematology, Oncology and Blood and Marrow Transplantation have adopted a standard protocol, informed by the consensus recommendations, for conducting pre-gene therapy assessments of patient readiness.

You can read the full consensus statement, Assessing Psychosocial Risk and Resilience to Support Readiness for Gene Therapy in Sickle Cell Disease: A Consensus Statement, in JAMA Network Open.

Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research.

Closing the ‘Valley of Death’: Pioneering – and paying for – new therapies

Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research

“To cure brain tumors, sickle cell disease and scores of other illnesses that have an outsized impact on pediatric patients, we will need an innovative mechanism to ensure that money is not a barrier to scientific advancement and world-class care,” says Dr. Bollard.

With the advent of life-changing cell and gene therapies (CGTs) to treat pediatric diseases, price is becoming a significant obstacle to care and cures.

Successful therapies can wind up shelved or in hard-to-reach clinical trials for a litany of reasons: high manufacturing costs, significant regulatory burdens, a lack of enthusiasm from the pharmaceutical industry in the small pediatric market and the simple fact that insurance companies resist paying the price of $1 million or more for a therapeutic. When successful treatments are set aside and become victims of this market failure, leaders in pediatric medicine say the drug has been relegated to the “Valley of Death.”

Experts at Children’s National Hospital and other leading U.S. research institutions are working to ferry drugs across it.

A new way forward

The Access4Kids think tank is bringing together healthcare leaders to chart another way – with its hosts Catherine Bollard, M.D., M.B.Ch.B., director of the Children’s National Center for Cancer and Immunology Research, Crystal Mackall, M.D., director of the Stanford Center for Cancer Cell Therapy, Julie Park, M.D., Oncology Department chair at St. Jude Children’s Research Hospital, and Alan Wayne, M.D., pediatrician-in-chief at Children’s Hospital Los Angeles. Organized at the Children’s National Research & Innovation Campus, the think tank will include voices from Seattle Children’s Hospital in Washington state and the Moonshot Presidential Office in Washington, D.C., along with experts from academic institutions, the federal government and patient advocacy groups.

They explained their vision in their recent Nature Medicine perspective,  “Enhancing pediatric access to cell and gene therapies.” One idea under consideration is to create a biotech enterprise – backed by public monies, foundations and philanthropies – to support the late-stage development and commercialization of pediatric CGTs. Called a Pediatric Advanced Medicines Biotech (PAMB), this new organization would follow a novel pathway outside the traditional biopharma development model.

“To cure brain tumors, sickle cell disease and scores of other illnesses that have an outsized impact on pediatric patients, we will need an innovative mechanism to ensure that money is not a barrier to scientific advancement and world-class care,” Dr. Bollard said. “My colleagues and I aren’t exaggerating when we say this is a ‘save the world’ effort. It’s an initiative to disrupt the pharmaceutical industry and impact medicine, ultimately saving lives and entire lifetimes.”

The think tank is the second in a series aimed at solving this formidable challenge. Led by scientists, the work goes to the heart of healthcare economics.

“We need to find a way to support the academic ecosystem by reducing costs, creating efficiencies in manufacturing and working with regulatory bodies to bolster business models that lead to safe and effective therapeutics,” Dr. Mackall said. “We went to school to study science and medicine. Now, our mission includes revamping business models, as we find ways to increase access to lifesaving treatments for children in need.”

Why it matters

Creating novel pathways to pay for CGTs presents a challenge and an opportunity for researchers in pediatrics and rare diseases. Drs. Mackall, Bollard and their colleagues are exasperated when scientists discover successful treatments for life-threatening illnesses, but market forces lock the drug away in hard-to-reach clinical trials or – even worse – land it on a shelf.

Consider just one example, laid out in the Nature Medicine perspective: Children with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) lack nearly all protection from viruses, bacteria and fungi, leaving them vulnerable to a world of opportunistic organisms. Researchers at San Raffaele Telethon Institute for Gene Therapy in Italy won U.S. and European regulatory approvals for a gene replacement therapy to treat the life-threatening disorder. Yet currently the therapy is only available in clinical trials, with support from research grants, philanthropic donations and institutional resources.

“This happens to successful therapeutics, and it’s heartbreaking. The current business model in medicine can lead to situations where successful therapies have extremely restricted availability, and there are no built-in guarantees of sustained access,” Dr. Bollard said. “We can and must do better – and we believe we have a way forward.”

graphic explaining LIFU and CAR T

Mission critical: Pentagon awards grant to combine two novel brain tumor therapies

graphic explaining LIFU and CAR TA Children’s National Hospital researcher is embarking on a two-year project that could revolutionize the care of rare pediatric brain tumors, through a Department of Defense (DOD) award to study the efficacy of combining the powers of acoustic therapy and cellular immunotherapy to treat the deadliest forms of medulloblastoma.

Designed by DOD to advance novel innovations that could revolutionize medicine, the prestigious Idea Award supports independent investigators with high-risk, but potentially high-reward, concepts to fill gaps in cancer prevention and treatment. Dalia Haydar, Pharm.D., Ph.D., principal investigator at the Cell Enhancement and Technologies for Immunotherapy Program, believes her first-of-its-kind approach could do just that.

A one-two punch

Dr. Haydar is building on promising research into a novel type of immunotherapy – chimeric antigen receptor (CAR) T-cell therapy – which uses the body’s own immune system to target and destroy pediatric brain tumors. She hopes to combine the potential of this immunotherapy with the early success seen in an acoustic therapy, called low-intensity focused ultrasound (LIFU). Akin to the imaging technology used during pregnancy, the sound waves can be directed toward any organ of the body for therapeutic reasons. With LIFU, Dr. Haydar hopes to tune the right amount of energy toward a brain tumor to temporarily open the blood-brain barrier and improve the delivery of therapeutics.

“We’re using two treatments that are tested in the clinic. We know how they work individually, but we’re investigating methods to combine the best aspects of both,” Dr. Haydar said. “I hope to use it, not just to open the channels in the blood-brain barrier, but also to cause a certain kind of immune response in the brain, which will help the CAR T-cells fight cancer.”

This collaborative grant includes experts in the field, including Yanxin Pei, Ph.D., principal investigator at Children’s National and an expert in medulloblastoma modeling, and Natasha Sheybani, Ph.D., assistant professor at the University of Virginia and a leading figure in the application of focused ultrasound.

Why we’re excited

Dr. Haydar is initially focused on high-risk medulloblastoma, specifically sonic hedgehog and group 3 subtypes, both of which are often fatal with existing chemotherapy and radiation treatments. Even when successful, the standard treatments can lead to life-long developmental side effects. Dr. Haydar hopes to show that the combined treatment improves survivorship, and she anticipates expanding her work to other types of pediatric brain tumors.

The $600,000 award shows the importance of well-resourced research institutions uniquely focused on pediatrics. Dr. Haydar noted that Children’s National is one of few research hospitals in the country with the necessary laboratory and ultrasound equipment on-site to develop a customizable treatment protocol. “We’re not just proposing to test this as a science project,” she said. “We’re proposing something that we can very well translate into the clinic and into a new approach for pediatric cancer patients.”

What we hope to discover

Through congressional funding, the Defense Department – one of the largest providers of pediatric healthcare for U.S. children – looks for opportunities to support the needs of military personnel and their dependents. Much of Dr. Haydar’s work will focus on determining safety and optimizing the delivery of the two treatments.

“You have to find the ideal timeline,” Dr. Haydar said. “Which therapy do you do first? How much spacing is best between them, and when do you repeat the therapy? What is the best dosing? It’s a puzzle, and I am hoping to solve it to give children with these often-fatal diagnoses a longer life – and a better one than existing treatments provide.”

researchers in a lab at Children's National

Pioneering gene therapy as a treatment for sickle cell disease

Gene therapy is a new and exciting treatment option available for patients with sickle cell disease (SCD). Children’s National Hospital is one of the few pediatric hospitals in the country that offers both FDA-approved sickle cell disease gene therapies: CASGEVY™ (exagamglogene autotemcel) and LYFGENIA™ (lovotibeglogene autotemcel).

What this means

Gene therapy involves an autologous transplant, taking the patient’s own stem cells, genetically changing those stem cells and then, after chemotherapy, infusing those stem cells back into the patient to make healthy blood.

“I’m excited about gene therapy for sickle cell disease. I think it has the potential to be a curative option for every single child with sickle cell disease,” said Robert Nickel, M.D., hematologist at Children’s National.

Currently both treatments are only approved for patients 12 years and older with severe disease. Children’s National was the first hospital in the world to collect stem cells for the LYFGENIA™ treatment.

Moving the field forward

Clinical trials hold incredible promise to advance the care of SCD. Children’s National continues to pioneer transplant therapies to cure SCD and is one of the leading centers participating in clinical trials of new treatments for this condition.

Experts at Children’s National are leading a multi-site clinical trial of a chemotherapy-free transplant approach for SCD using a matched sibling donor. This chemotherapy-free approach has less toxicity and side effects for children undergoing transplant.

In addition, Children’s National has been leading the way with innovative approaches to support sickle cell patients. “We’re providing alternative approaches to pain such as healing touch, acupuncture, massage VR technology, physical therapy and exploring other ways of treating pain in an integrated manner,” said Andrew Campbell, M.D., director of the Comprehensive Sickle Cell Disease Program at Children’s National.

The team is also exploring non-opioid treatments, such as intravenous citrulline, a naturally occurring amino acid that has been proven to enhance blood flow and potentially alleviate pain in treated patients in preliminary studies under the direction of Suvankar Majumdar, M.D., chief of Hematology at Children’s National.

illustration of sickled blood cells

Children’s National experts showcase sickle cell disease research

illustration of sickled blood cellsAndrew Campbell, M.D., director of the Comprehensive Sickle Cell Disease program, assessed the lifetime value of cell and gene therapy (CGTS) through a case study at The American Society of Gene and Cell Therapy’s (ASGCT) Annual Meeting.

Dr. Campbell and other Children’s National researchers will be presenting again at the Foundation for Sickle Cell Disease Research’s (FSCDR) Annual Sickle Cell Disease Research and Educational Symposium, June 7-9, 2024. The symposium includes more than 500 leading researchers, physicians, clinicians and social workers from all over the world.

Here’s a look at the presentations from Children’s National:

Day Time Presenter(s) Title
Sunday, June 9, 2024 8:00 AM – 9:15 AM Andrew Campbell, M.D. Update on Sickle Cell Legislation in the US

 
Sunday, June 9, 2024 3:00 PM – 3:15 PM Andrew Campbell, M.D., Deepika Darbari, M.D., and Regine Hyppolite, MSA Diagnostic Potential of Platelet-Neutrophil Ratio (PNR) for Stroke Risk in SCD Children

 
Sunday, June 9, 2024 3:15 PM – 3:30 PM

 

 Andrew Campbell, M.D. A Pilot Study to Increase Naloxone Education and Prescriptions in Sickle Cell Clinics

 
Sunday, June 9, 2024 4:00 PM – 4:15 PM Steven Hardy, Ph.D. Correlation Between VOC and Cognitive Function Using The NIH ToolBox in SCD
Sunday, June 9, 2024 4:15 PM – 4:30 PM

 

 

 Andrew Campbell, M.D., Deepika Darbari, M.D., and Regine Hyppolite, MSA Platelet to neutrophil ratio as a novel marker for monitoring SCD patients on hydroxyurea

 

 

Marius George Linguraru giving a lecture on AI

Artificial – and accelerated – intelligence: endless applications to expand health equity

In the complex world of pediatric diseases, researchers need access to data to develop clinical trials and the participation of vulnerable patients to develop new devices and therapies. Both are in short supply, given that most children are born healthy, and most severe pediatric diseases are rare.

That creates a dilemma: how do researchers build a foundation to advance new treatments? Enter artificial intelligence (AI).

“AI is the equalizer: accelerated intelligence for sick kids. No other advance on the horizon holds more promise for improving equity and access to pediatric healthcare when diseases are rare and resources are limited,” says Marius George Linguraru, D.Phil., M.A., M.Sc., the Connor Family Professor in Research and Innovation and principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI). “AI will shrink the distance between patient and provider, allowing our physicians and scientists to provide targeted healthcare for children more efficiently. The possibilities are endless.”

Why we’re excited

By pioneering AI innovation programs at Children’s National Hospital, Dr. Linguraru and the AI experts he leads are ensuring patients and families benefit from a coming wave of technological advances. The team is teaching AI to interpret complex data that could otherwise overwhelm clinicians. Their work will create systems to identify at-risk patients, forecast disease and treatment patterns, and support complex clinical decisions to optimize patient care and hospital resources. Already, the AI team at SZI has developed data-driven tools touching nearly every corner of the hospital:

  • AI for rheumatic heart disease (RHD): In partnership with Children’s National cardiology leaders, including Craig Sable, M.D., the Uganda Heart Institute and Cincinnati Children’s Hospital, the AI team has developed an algorithm that can use low-cost, portable ultrasound imaging to detect RHD in children and young adults, a disease that takes nearly 400,000 lives annually in limited-resource countries. Early testing shows the AI platform has the same accuracy as a cardiologist in detecting RHD, paving the way for earlier treatment with life-saving antibiotics. This year, Children’s National physicians will be in Uganda, screening 200,000 children with local cardiology experts and AI technology.
  • Newborn screening for genetic conditions with mGene: Working with Rare Disease Institute clinicians and Chief of Genetics and Metabolism Debra Regier, M.D., the AI team has built technology to detect rare genetic disorders, using an algorithm and a smartphone camera to identify subtle changes in facial features. Tested on patients from over 30 countries and published in The Lancet Digital Health, the application helps screen children for advanced care when a geneticist may not be within reach. With funding from the National Institutes of Health, Children’s National and its research partners are piloting a newborn screening program in the Democratic Republic of the Congo.
  • Pediatric brain tumors: To improve and personalize the treatment decisions for children with brain tumors, Dr. Linguraru’s team is working with Brain Tumor Institute Director Roger Packer, M.D., the Gilbert Family Distinguished Professor of Neurofibromatosis, on algorithms that can characterize and measure brain tumors with unprecedented precision. The team recently won the International Pediatric Brain Tumor Segmentation Challenge, distinguishing the Children’s National algorithm as among the best in the world.
  • Ultra-low field magnetic resonance imaging (MRI): With a grant from the Bill & Melinda Gates Foundation, the AI team is working alongside Children’s Hospital Los Angeles, King’s College London and the UNITY Consortium to expand global brain imaging capacity. The consortium is helping clinicians in limited-resource countries improve the treatment of neonatal neurological conditions, using AI to boost the quality of ultra-low field MRI and expand access to this portable and more affordable imaging option.
  • Federated learning: Children’s National has collaborated with NVIDIA and other industry leaders to accelerate AI advances through federated learning. Under this approach, institutions share AI models rather than data, allowing them to collaborate without exposing patient information or being constrained by essential data-sharing restrictions. The SZI team was the only pediatric partner invited to join the largest federated learning project of its kind, studying the lungs of COVID-19 patients. Details were published in Nature Medicine.

Children’s National leads the way

Looking ahead, the Children’s National AI team is pursuing a wide range of advances in clinical care. To support patients treated at multiple clinics, they are developing systems to harmonize images from different scanners and protocols, such as MRI machines made by different manufacturers. Similar work is underway to analyze pathology samples from different institutions consistently.

Automation is also making care more efficient. For example, using data from 1 million chest X-rays, the team is collaborating with NVIDIA to develop a conversational digital assistant that will allow physicians to think through 14 possible diagnoses.

Dr. Linguraru says he and his colleagues are galvanized by the jarring statistic that one in three children with a rare disease dies before age 5. While well-implemented AI initiatives can change outcomes, he says the work must be done thoughtfully.

“In the future, patients will be evaluated by human clinicians and machines with extraordinary powers to diagnose illness and determine treatments,” Dr. Linguraru said. “Our team at Children’s National is leading conversations about the future of pediatric healthcare with a focus on safety, resource allocation and basic equity.”

Learn more about our AI initiatives

Innovation leaders at Children’s National Hospital are building a community of AI caregivers through educational and community-building events. At the inaugural Symposium on Artificial Intelligence in 2023 at the Children’s National Research & Innovation Campus, experts from Virginia Tech, JLABS, Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere laid out a vision for using data to advance pediatric medicine. The symposium will return on Sept. 6.

Dr. Linguraru is the program chair of MICCAI 2024, the top international meeting on medical image computing and computer-assisted intervention and the preeminent forum for disseminating AI developments in healthcare. The conference is an educational platform for scientists and clinicians dedicated to AI in medical imaging, with a focus on global health equity. It will take place for the first time in Africa on Oct. 6-10.

 

 

teenager receiving an intravenous infusion

Novel cell therapy treatments offer promise to immune-compromised children

teenager receiving an intravenous infusion

In a first-of-its-kind clinical trial, researchers found that intravenous therapies made from virus-specific T-cells (VST) can effectively treat immunocompromised pediatric patients, far surpassing the current standard of care, according to new research published in Nature Communications.

More than 60% of patients in the phase 2 clinical trial led by investigators from Children’s National Hospital and Huntsman Cancer Institute responded to the innovative VST therapy. This new treatment uses blood from healthy donors to manufacture a highly specialized immune therapy that, when given to immune-compromised patients, prompts their immune system to fight off potentially life-threatening viruses, including cytomegalovirus, Epstein-Barr and adenovirus. Without this therapy, estimates suggest that less than 30% of patients would recover, using standard protocols.

“A vast majority of our patients not only responded to the therapy, but they were able to come off their antivirals, which come with extensive side effects,” said Michael Keller, M.D., the paper’s first author and the Translational Research Laboratory director at the Children’s National Cell Enhancement and Technologies for Immunotherapy (CETI) program. “This promising data suggests hope for patients with rare immune-compromising diseases that leave them vulnerable to so much in the world.”

The study brings together experts from the Pediatric Transplantation and Cell Therapy Consortium (PTCTC) and the Primary Immune Deficiency Treatment Consortium (PIDTC) to create the first multi-center, pediatric-consortium trial of adoptive T-cell therapies for viruses. It also represents one of the first to include critically ill patients, who are often excluded from research.

Children’s National leads the way

Working alongside Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research (CCIR), Dr. Keller and the CCIR team helped build an internationally recognized program, pioneering therapies to prevent complications from viral infections in immunocompromised patients. This includes patients with congenital immune deficiency and others who have undergone bone marrow transplantation for malignancies or non-malignant conditions, such as sickle cell disease.

While doctors can treat some immune-compromised patients for infections with standard antivirals, a small fraction don’t respond. Children’s National is one of a handful of hospitals in the country that has options. Over the last several decades, researchers have found ways to develop VST therapies made from banked T-cells, a more advanced application of how donated red blood cells are used to treat anemia.

In 2017, Drs. Keller and Bollard started collaborating with Michael Pulsipher, M.D.—now with Intermountain Primary Children’s Hospital and the Huntsman Cancer Institute at the University of Utah—to create a multi-institute clinical study. They combined the expertise at Children’s National in producing and banking cell therapy products with the community built around the PTCTC. Ultimately, they launched a clinical trial that was open to 35 centers in the U.S., enrolling 51 patients at 22 hospitals from 2018-2022.

“We wanted to prove that this potentially life-saving therapy could be given safely at regional pediatric centers that had never been able to use this approach before,” said Dr. Pulsipher, who served as the study’s co-principal investigator with Dr. Keller. “We united top experts in this area from the PTCTC and PIDTC and successfully treated some of the most challenging patients ever treated with this approach. Our findings helped define who can benefit the most from this therapy, paving the way for commercial development.”

The Good Manufacturing Practices (GMP) laboratory at Children’s National, led by Patrick Hanley, Ph.D., provided suitable VST therapies for 75 of 77 patients who requested to join the study. Clinical responses were achieved in 62% of patients who underwent stem cell transplants and in 73% of patients who were treated with VST and evaluated one month after their infusion. The paper laid out risks and clinical factors impacting outcomes when third-party donors are used to manufacture the VST therapies.

What’s ahead

Given that researchers are only beginning to develop cell therapies, work remains to understand the many ways they interact with the immune system. In a separate paper also recently published in Nature Communications, members of the multi-institute team documented a case of an infant with severe combined immune deficiency, who faced extremely rare side effects when the VST treatment interfered with her donor bone marrow graft. The case led the team to work with the Food and Drug Administration to identify criteria for VST donors enrolled in this study to mitigate complications.

In the decade ahead, Dr. Bollard sees promise in cell therapies for patients with cancer, immune deficiencies after transplant and dozens of other disorders, including genetic and autoimmune diseases. “Future studies will continue to look at ways to optimize the manufacturing, the administration and the long-term outcomes for these therapies—and to enhance the lifelong impact on our patients,” she said. “When we pair human ingenuity with the power of technology, I see tremendous potential.”

Acknowledgments: This study was funded with a nearly $5 million grant from the California Institute of Regenerative Medicine and was run through the operations center at the Children’s Hospital of Los Angeles, where Dr. Pulsipher was formerly on faculty.

desktop computer showing the CNRI Annual Report

Driving pediatric breakthroughs through 2023

desktop computer showing the CNRI Annual ReportThe Children’s National Research Institute released its 2022-2023 Academic Annual Report. In the report, a summary of the past academic year highlights the accomplishments of each of the institute’s research centers, provides research funding figures and exalts some of the institute’s biggest milestones.

The stories in the report are a testament to the hard work and dedication of everyone at the Children’s National Research Institute.

We celebrated five decades of leadership and mentorship of Naomi Luban, M.D., and her incredible accomplishments in the W@TCH program, which have been instrumental in shaping the future of pediatric research.

We also celebrated innovation, highlighting our recent FDA award to lead a pediatric device consortium, which recognizes our commitment to developing innovative medical devices that improve the lives of children.

Breakthroughs at the Research & Innovation Campus continued as our researchers worked tirelessly to develop new treatments and therapies that will transform the lives of children and families around the world.

Taking a look at the breakthroughs happening in our now six research centers, we spotlighted the following stories:

  • Reflecting on decades of progress in the blood, marrow and cell therapy programs at Children’s National. Our researchers have made significant strides in this field, and we are proud to be at the forefront of these life-saving treatments.
  • In genetic medicine, we continue to be a beacon of hope for families facing rare and complex conditions. Our researchers are making incredible breakthroughs that are changing the landscape of pediatric medicine.
  • We are also proud to share the $90 million award received from an anonymous donor to support pediatric brain tumor research. The predominant focus of this award is to develop new treatments that will improve outcomes for children with this devastating disease.
  • This year, we opened a new Center that enhances our research capabilities in the field of Prenatal, Neonatal & Maternal Health Research. We are excited about the possibilities this new center will bring and look forward to the discoveries that will emerge from it.
  • In addition, we are driving future pandemic readiness with the NIH funded Pediatric Pandemic Network. Our researchers are using cutting-edge technology and innovative approaches to prepare for the next pandemic and protect children.
  • We are also exploring the potential of artificial intelligence (AI) in pediatric breakthroughs. Our researchers are using machine learning and other AI techniques to develop new treatments and therapies that will transform the lives of children.
collage of news outlet logos

Children’s National in the News: 2023

collage of news outlet logos
Explore some of the notable medical advancements and stories of bravery that defined 2023, showcasing the steadfast commitment of healthcare professionals at Children’s National Hospital and the resilient spirit of the children they support. Delve into our 2023 news highlights for more.

1. COVID during pregnancy dramatically increases the risk of complications and maternal death, large new study finds

According to a study published in British Medical Journal Global Health, women who get COVID during pregnancy are nearly eight times more likely to die and face a significantly elevated risk of ICU admission and pneumonia. Sarah Mulkey, M.D., prenatal-neonatologist neurologist, discussed findings based on her work with pregnant women and their babies.
(Fortune)

2. Rest isn’t necessarily best for concussion recovery in children, study says

A study led by Christopher Vaughan, Psy.D., pediatric neuropsychologist, suggests that — despite what many people may presume — getting kids back to school quickly is the best way to boost their chance for a rapid recovery after a concussion.
(CNN)

3. Pediatric hospital beds are in high demand for ailing children. Here’s why

David Wessel, M.D., executive vice president, chief medical officer and physician-in-chief, explained that one reason parents were still having trouble getting their children beds in a pediatric hospital or a pediatric unit after the fall 2022 respiratory surge is that pediatric hospitals are paid less by insurance.
(CNN)

4. Anisha Abraham details impact of social media use on children: ‘True mental health crisis’

Anisha Abraham, M.D., M.P.H., chief of the Division of Adolescent and Young Adult Medicine, joined America’s Newsroom to discuss the impact social media access has had on children’s mental health.
(FOX News)

5. Saving Antonio: Can a renowned hospital keep a boy from being shot again?

After 13-year-old Antonio was nearly killed outside his mom’s apartment, Children’s National Hospital went beyond treating his bullet wounds. Read how our Youth Violence Intervention Program team supported him and his family during his recovery.
(The Washington Post)

6. Formerly conjoined twins reunite with doctors who separated them

Erin and Jade Buckles underwent a successful separation at Children’s National Hospital. Nearly 20 years later they returned to meet with some of the medical staff who helped make it happen.
(Good Morning America)

7. Asthma mortality rates differ by location, race/ethnicity, age

Shilpa Patel, M.D., M.P.H., medical director of the Children’s National IMPACT DC Asthma Clinic, weighed in on a letter published in Annals of Allergy, Asthma & Immunology, asserting that the disparities in mortality due to asthma in the United States vary based on whether they occurred in a hospital, ethnicity or race and age of the patient.
(Healio)

8. How one Afghan family made the perilous journey across the U.S.-Mexico border

After one family embarked on a perilous journey from Afghanistan through Mexico to the U.S.-Mexico border, they eventually secured entry to the U.S. where Karen Smith, M.D., medical director of Global Services, aided the family’s transition and provided their daughter with necessary immediate medical treatment.
(NPR)

9. When a child is shot, doctors must heal more than just bullet holes

With the number of young people shot by guns on the rise in the U.S., providers and staff at Children’s National Hospital are trying to break the cycle of violence. But it’s not just the physical wounds though that need treating: young victims may also need help getting back on the right track — whether that means enrolling in school, finding a new group of friends or getting a job.
(BBC News)

10. This 6-year-old is a pioneer in the quest to treat a deadly brain tumor

Callie, a 6-year-old diagnosed with diffuse intrinsic pontine glioma, was treated with low-intensity focused ultrasound (LIFU) at Children’s National Hospital and is the second child in the world to receive this treatment for a brain tumor. LIFU is an emerging technology that experts like Hasan Syed, M.D., and Adrianna Fonseca, M.D., are trialing to treat this fatal childhood brain tumor.
(The Washington Post)

11. F.D.A. approves sickle cell treatments, including one that uses CRISPR

The FDA approved a new genetic therapy, giving people with sickle cell disease new opportunities to eliminate their symptoms. David Jacobsohn, M.B.A., M.D., confirmed that Children’s National Hospital is one of the authorized treatment centers and talked about giving priority to the sickest patients if they are on Vertex’s list.
(The New York Times)

12. 6-year-old fulfils wish to dance in the Nutcracker

After the potential need for open-heart surgery threatened Caroline’s Nutcracker performance, Manan Desai, M.D., a cardiac surgeon, figured out a less invasive procedure to help reduce her recovery time so she could perform in time for the holidays.
(Good Morning America)

2023 with a lightbulb

The best of 2023 from Innovation District

2023 with a lightbulbAdvanced MRI visualization techniques to follow blood flow in the hearts of cardiac patients. Gene therapy for pediatric patients with Duchenne muscular dystrophy. 3D-printed casts for treating clubfoot. These were among the most popular articles we published on Innovation District in 2023. Read on for our full list.

1. Advanced MRI hopes to improve outcomes for Fontan cardiac patients

Cardiac imaging specialists and cardiac surgeons at Children’s National Hospital are applying advanced magnetic resonance imaging visualization techniques to understand the intricacies of blood flow within the heart chambers of children with single ventricle heart defects like hypoplastic left heart syndrome. The data allows surgeons to make critical corrections to the atrioventricular valve before a child undergoes the single ventricle procedure known as the Fontan.
(3 min. read)

2. Children’s National gives first commercial dose of new FDA-approved gene therapy for Duchenne muscular dystrophy

Children’s National Hospital became the first pediatric hospital to administer a commercial dose of Elevidys (delandistrogene moxeparvovec-rokl), the first gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD). Elevidys is a one-time intravenous gene therapy that aims to delay or halt the progression of DMD by delivering a modified, functional version of dystrophin to muscle cells.
(2 min. read)

3. New model to treat Becker Muscular Dystrophy

Researchers at Children’s National Hospital 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. The work provides scientists with a much-needed method to identify, develop and de-risk drugs for patients with BMD.
(2 min. read)

4. First infants in the U.S. with specially modified pacemakers show excellent early outcomes

In 2022, five newborns with life-threatening congenital heart disease affecting their heart rhythms were the first in the United States to receive a novel modified pacemaker generator to stabilize their heart rhythms within days of birth. Two of the five cases were cared for at Children’s National Hospital. In a follow-up article, the team at Children’s National shared that “early post-operative performance of this device has been excellent.”
(2 min. read)

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

Experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere came together to discuss how pediatric specialties can use AI to provide medical care to kids more efficiently, more quickly and more effectively 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.
(3 min. read)

6. AAP names Children’s National gun violence study one of the most influential articles ever published

The American Academy of Pediatrics (AAP) named a 2019 study led by clinician-researchers at Children’s National Hospital one of the 12 most influential Pediatric Emergency Medicine articles ever published in the journal Pediatrics. The findings showed that states with stricter gun laws and laws requiring universal background checks for gun purchases had lower firearm-related pediatric mortality rates but that more investigation was needed to better understand the impact of firearm legislation on pediatric mortality.
(2 min. read)

7. Why a colorectal transition program matters

Children’s National Hospital recently welcomed pediatric and adult colorectal surgeon Erin Teeple, M.D., to the Division of Colorectal and Pelvic Reconstruction. Dr. Teeple is the only person in the United States who is board-certified as both a pediatric surgeon and adult colorectal surgeon, uniquely positioning her to care for people with both acquired and congenital colorectal disease and help them transition from pediatric care to adult caregivers.
(3 min. read)

8. First-of-its-kind holistic program for managing pain in sickle cell disease

The sickle cell team at Children’s National Hospital received a grant from the Founders Auxiliary Board to launch a first-of-its-kind, personalized holistic transformative program for the management of pain in sickle cell disease. The clinic uses an inter-disciplinary approach of hematology, psychology, psychiatry, anesthesiology/pain medicine, acupuncture, mindfulness, relaxation and aromatherapy services.
(3 min read)

9. Recommendations for management of positive monosomy X on cell-free DNA screening

Non-invasive prenatal testing using cell-free DNA (cfDNA) is currently offered to all pregnant women regardless of the fetal risk. In a study published in the American Journal of Obstetrics and Gynecology, researchers from Children’s National Hospital provided context and expert recommendations for maternal and fetal evaluation and management when cfDNA screening is positive for monosomy X or Turner Syndrome.
(2 min. read)

10. Innovation in clubfoot management using 3D anatomical mapping

While clubfoot is relatively common and the treatment is highly successful, the weekly visits required for Ponseti casting can be a significant burden on families. Researchers at Children’s National Hospital are looking for a way to relieve that burden with a new study that could eliminate the weekly visits with a series of 3D-printed casts that families can switch out at home.
(1 min. read)

11. Gender Self-Report seeks to capture the gender spectrum for broad research applications

A new validated self-report tool provides researchers with a way to characterize the gender of research participants beyond their binary designated sex at birth. The multi-dimensional Gender Self-Report, developed using a community-driven approach and then scientifically validated, was outlined in a peer-reviewed article in the American Psychologist, a journal of the American Psychological Association.
(2 min. read)

12. Cardiovascular and bone diseases in chronic kidney disease

In a study published by Advances in Chronic Kidney Disease, a team at Children’s National Hospital reviewed cardiovascular and bone diseases in chronic kidney disease and end-stage kidney disease patients with a focus on pediatric issues and concerns.
(1 min. read)