Children’s National scientists excel in brain cancer, genetics and neuroscience.Credit: Children’s National Hospital
Just north of the city centre in Washington, DC, Children’s National Hospital has created an ecosystem of experts and information at the Children’s National Research & Innovation Campus (RIC).
“We focus on research that leads to new therapeutics, new therapeutic interventions and innovation in paediatric care and paediatric research,” says Vittorio Gallo, chief academic officer and director of the Children’s National Research Institute (CNRI). “We’re also aligned with the ultimate mission of Children’s National, which is to improve healthcare for our children and their families.”
It’s a noble goal, and no easy task. Paediatric innovation in the United States has fallen far behind medical advances benefiting adult patients. Americans under the age of 18 make up nearly a quarter of the country’s population, but only about 10% of funding from the U.S. National Institutes of Health supports paediatric research1. There’s also a lack of support for paediatric device innovation. Over the past 14 years, only 24% of Class III life-saving devices approved by FDA were for paediatric use.
Closing the gap requires a single-minded approach to paediatric research and innovation. Children’s National scientists and clinicians excel in brain cancer, genetics and neuroscience, but the institution amplifies its impact through collaboration.
The Center for Genetic Medicine Research, the Rare Disease Institute and molecular diagnostics labs at Children’s National work together to develop precision medicine based on paediatric genomic research. “We have one of the largest clinical genetics programmes in the nation, and probably the largest paediatric genetics programme in the nation,” Gallo says. “One of our strengths comes from the opportunity to serve a large paediatric population, which is the basis for our research programmes.” That combination of institutional expertise creates a unique ecosystem for quickly pursuing promising research, and translating it into new treatments.
But the campus doesn’t work in isolation. CNRI creates bench-to-bedside improvements in children’s health by gathering key partners, including the likes of Virginia Tech and the Johnson & Johnson Innovation – JLABS network of incubators, which supports start-up companies working on new pharma, medtech and health-related technology.
The location of Children’s National and the RIC bolsters other key connections, such as working with the Food and Drug Administration (FDA) and National Institutes of Health (NIH). “We have access to advocacy groups, and we’re very strongly integrated with the nation’s capital and Washington, DC government,” Gallo says. “We’ve also had many programmes that serve DC public schools.” Some of that work focuses on reducing disparities in children’s health.
By working with so many groups and gathering so many experts, Children’s National has fostered a culture of collaboration. “Team science is at the core of what we do,” says Catherine Bollard, director of the Center for Cancer and Immunology Research at CNRI. “We are in this unique situation to be able to see the patients in the clinic and then also go back to the bench to figure out how to help them.”
This culture of collaboration includes philanthropic partners such as the United Arab Emirates, which contributed US$30 million in 2018 to help establish the campus.
Teaming up on solid tumours
Scientists at the Center for Cancer and Immunology Research are exploring many ways to modify T cells to attack solid tumours. Paediatric oncologist Holly Meany is studying the use of tumour-associated antigen-specific T cells to create precision treatments for paediatric solid tumours outside the central nervous system. This project, among others, aims to engineer T cells or other immune cells to target a specific tumour and kill it.
Children’s National researchers are also participating in a US$25 million Cancer Grand Challenges award from Cancer Research UK and the US National Cancer Institute. Bollard – who co-leads this project with Martin Pule, clinical associate professor at University College London – says the international team is “focused on targeting solid tumours and developing novel cell therapies for children”.
The project will include identifying targets to attack with T-cell therapies. “We brought this team together with a common vision, which is to make these sorts of T-cell therapies the standard of care for these patients in the next decade,” says Bollard. Those treatments will advance care for a wide range of paediatric solid tumours.
By gathering expertise and working with external partners, the Children's National Research Institute creates bench-to-bedside improvements in children’s health.Credit: Children’s National Hospital
New hope against inoperable brain cancer
Another research partnership has seen academics from Virginia Tech team up with Children’s National in search of new ways to treat diffuse intrinsic pontine glioma (DIPG) and glioblastoma multiforme, particularly devastating forms of brain cancer. DIPG starts in the pons, which lies in the brainstem and plays a crucial role in respiration. As the name implies, this cancer grows into a disseminated network of cells, instead of a concentrated clump. “It’s virtually inoperable,” says Michael Friedlander, executive director of the Fralin Biomedical Research Institute and vice president for health sciences and technology at Virginia Tech.
The median survival time for DIPG is about 11 months, and only 10% of patients live for two years2. There is no cure. “It’s just a heartbreaking diagnosis to tell parents,” says Bollard.
Virginia Tech is collaborating with Children’s National to find cellular and molecular treatments that kill DIPG cells. Even with these treatments, however, getting them to the cancer is a challenge. “The blood-brain barrier stops the drugs from reaching the target,” Friedlander says. “You could inject the therapeutic agent directly into the brain, but that takes surgery.”
Instead, Virginia Tech assembled a group of biomedical engineers, neuroscientists and veterinary neurologists to see if focused ultrasound could solve the problem. “This technology opens up the blood-brain barrier transiently,” Friedlander says. “The goal is to deliver a therapeutic drug intravenously to get it in and treat a brain tumour.” When the focused ultrasound is turned off, the blood-brain barrier resumes its protective role.
Combining targeted treatments with a novel method of drug delivery could give new hope to children with DIPG.
New insights in neuroscience
While Friedlander’s team works on delivering drugs to the brain, CNRI’s renowned neuroscientists are generating other insights into the body’s most complex and mysterious organ.
Some of this work is dedicated to investigating the root causes of brain tumours, and how best to treat them. Neuro-oncologists at the CNRI Center for Neuroscience Research conduct a range of basic and clinical research on brain tumours, from the basic biology and genetic causes through pathophysiology and developing targeted treatments. Some of these scientists work on the National Cancer Institute’s Pediatric Brain Tumor Consortium, a multi-centre study focused on developing new treatments for paediatric tumours in the central nervous system. “We are very strong in paediatric brain tumours and cell immunotherapy,” Gallo says.
As well as finding new ways to treat cancer, neuroscientists at Children’s National study neurodevelopmental disabilities. “Many of us are focused on the events that occur before birth and how brain development and function transition from birth into childhood and cognitive function thereafter,” says CNRI Center for Neuroscience Research director Tarik Haydar.
As an example, Haydar is working with partners to discover more about how Down syndrome – which arises from a trisomy, or having an extra copy of a chromosome – affects brain function. It’s a project grounded a 2016 study of the disorder by Haydar and colleagues, which shed new light on genome-wide alternations in the expression of a large number of genes that they observed in affected brains3.
“The cells that make the insulation in the brain are affected by the trisomy in a way that hadn’t been seen before that study,” says Haydar. The team’s conclusion that the trisomy diminishes the number of mature cells of this type provided a clue about the impact of Down syndrome. “Since that insulation is what allows quick communication, changes in that component of the nervous system could influence intellectual functioning,” Haydar says. Now, Haydar and his colleagues want to know how they can make the best use of that information to help these cells mature properly.
More exciting work on neurological disorders lies ahead for Haydar and his colleagues at the RIC. In 2021, Children’s National received an NIH grant to expand the DC Intellectual and Developmental Disabilities Research Center and relocate it to the campus. At this facility, scientists take a multidisciplinary approach to studying the basic biology and potential treatments for a wide range of developmental disabilities, from autism and cerebral palsy to epilepsy and inherited metabolic disorders.
The path to the clinic
Through all of these connected programmes and projects, Children’s National puts a premium on creating new approaches to enhance paediatric healthcare. But new ideas are only worthwhile if they have an impact on real clinical outcomes.
“Our Innovation Ventures Program, led by Kolaleh Eskandanian, is really focused on bringing new therapeutics and new devices to paediatric clinical care,” Gallo says. “We rapidly take technology, or a therapy or a device, from concept to implementation to the marketplace, where new discoveries can benefit children.”
In fact, a key objective of the RIC is nurturing innovation. Gallo offers the the Johnson & Johnson Innovation – JLABS network as a prime example. “JLABS can offer our investigators networking and access to innovative start-up companies.”
“Johnson & Johnson Innovation opened JLABS @ Washington, DC – our 13th life science incubator location – as part of our vision to help accelerate scientific innovation for patients with unmet needs and in underserved populations,” says Sally Allain, head of Johnson & Johnson Innovation – JLABS @ Washington, DC. “This state-of-the-art site is committed to innovation across the healthcare spectrum, and our partnership with Children’s National Hospital seeks solutions for our tiniest patients. We are just beginning to exemplify the transformative power of this strategic collaboration. Together, we hope to build a flourishing ecosystem for all of healthcare and paediatric innovation.”
At the heart of American policymaking and regulation, Children’s National is in a position to amplify its impact on paediatric healthcare. “Here in Washington, we have a leading role, not only at the local level, but also the national and international levels,” Gallo says. Ongoing projects at the RIC promise to strengthen that role even further.