Genetics & Rare Diseases

Dr. Matthew Bramble, Vincent Kambale, and Neerja Vashist

Gut microbiome may impact susceptibility to konzo

Dr. Matthew Bramble, Vincent Kambale, and Neerja Vashist

From left to right: Dr. Matthew Bramble, Vincent Kambale, and Neerja Vashist. Here, the team is processing samples in the field collected from the study cohort prior to storage in liquid nitrogen. Bramble et al. Nature Communications (2021).

Differences between gut flora and genes from konzo-prone regions of the Democratic Republic of Congo (DRC) may affect the release of cyanide after poorly processed cassava is consumed, according to a study with 180 children. Cassava is a food security crop for over half a billion people in the developing world. Children living in high-risk konzo areas have high glucosidase (linamarase) microbes and low rhodanese microbes in their gut, which could mean more susceptibility and less protection against the disease, suggest Children’s National Hospital researchers who led the study published in Nature Communications.

Konzo is a severe, irreversible neurologic disease that results in paralysis. It occurs after consuming poorly processed cassava — a manioc root and essential crop for DRC and other low-income nations. Poorly processed cassava contains linamarin, a cyanogenic compound. While enzymes with glucosidase activity convert starch to simple sugars, they also break down linamarin, which then releases cyanide into the body.

Neerja Vashist learning how to make fufu

Neerja Vashist is learning how to make fufu. Fufu is a traditional food made from cassava flour, and the cassava flour used in the making of the fufu here has gone through the wetting method to further remove toxins from the cassava flour prior to consumption. Bramble et al. Nature Communications (2021).

“Knowing who is more at risk could result in targeted interventions to process cassava better or try to diversify the diet,” said Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research at Children’s National. “An alternative intervention is to modify the microbiome to increase the level of protection. This is, however, a difficult task which may have unintended consequences and other side effects.”

The exact biological mechanisms underlying konzo disease susceptibility and severity remained poorly understood until now. This is the first study to shed light on the gut microbiome of populations that rely on toxic cassava as their primary food source.

“While the gut microbiome is not the sole cause of disease given that environment and malnourishment play a role, it is a required modulator,” said Matthew S. Bramble, Ph.D., staff scientist at Children’s National. “Simply stated, without gut microbes, linamarin and other cyanogenic glucosides would pose little to no risk to humans.”

To understand the influence of a detrimental subsistence on the gut flora and its relationship to this debilitating multifactorial neurological disease, the researchers compared the gut microbiome profiles in 180 children from the DRC using shotgun metagenomic sequencing. This approach evaluates bacterial diversity and detects the abundance of microbes and microbial genes in various environments.

The samples were collected in Kinshasa, an urban area with diversified diet and without konzo; Masi-Manimba, a rural area with predominant cassava diet and low prevalence of konzo; and Kahemba, a region with predominant cassava diet and high prevalence of konzo.

Dr. Nicole Mashukano and Dr. Matthew Bramble wetting cassava flour

From left to right: Dr. Nicole Mashukano and Dr. Matthew Bramble. Dr. Mashukano leads the efforts in Kahemba to teach the wetting method to individuals in different health zones. The wetting method is used as an additional step to further detoxify toxins from cassava flour prior to consumption. Here, Dr. Mashukano and Dr. Bramble are spreading out the wet mixture of cassava flour and water into a thin layer on a tarp for drying in the sun, which allows cyanogen breakdown and release in the form of hydrogen cyanide gas. Bramble et al. Nature Communications (2021).

“This study overcame many challenges of doing research in low-resource settings,” said Desire Tshala-Katumbay, M.D., M.P.H., Ph.D., FANA, co-senior author and expert scientist at Institut National de Recherche Biomédicale in Kinshasa, DRC, and professor of neurology at Oregon Health & Science University. “It will open novel avenues to prevent konzo, a devastating disease for many children in Sub-Saharan Africa.”

For next steps, the researchers will study sibling pairs from konzo-prone regions of Kahemba where only one sibling is affected with the disease.

“Studying siblings will help us control for factors that cannot be controlled otherwise, such as the cassava preparation in the household,” said Neerja Vashist, Ph.D. candidate and research trainee at Children’s National. “In this work, each sample had approximately 5 million DNA reads each, so for our follow-up, we plan to increase that to greater than 40 million reads per sample and the overall study cohort size. This study design will allow us to confirm that the trends we observed hold on a larger scale, while enhancing our ability to comprehensively characterize the gut microbiome.”

control population and population with Williams-Beuren syndrome.

Machine learning tool detects the risk of genetic syndromes

control population and population with Williams-Beuren syndrome.

(A) Control population. (B) Population with Williams-Beuren syndrome. Average faces were generated for each demographic group after automatic face pose correction.

With an average accuracy of 88%, a deep learning technology offers rapid genetic screening that could accelerate the diagnosis of genetic syndromes, recommending further investigation or referral to a specialist in seconds, according to a study published in The Lancet Digital Health. Trained with data from 2,800 pediatric patients from 28 countries, the technology also considers the face variability related to sex, age, racial and ethnic background, according to the study led by Children’s National Hospital researchers.

“We built a software device to increase access to care and a machine learning technology to identify the disease patterns not immediately obvious to the human eye or intuition, and to help physicians non-specialized in genetics,” said Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital and senior author of the study. “This technological innovation can help children without access to specialized clinics, which are unavailable in most of the world. Ultimately, it can help reduce health inequality in under-resourced societies.”

This machine learning technology indicates the presence of a genetic syndrome from a facial photograph captured at the point-of-care, such as in pediatrician offices, maternity wards and general practitioner clinics.

“Unlike other technologies, the strength of this program is distinguishing ‘normal’ from ‘not-normal,’ which makes it an effective screening tool in the hands of community caregivers,” said Marshall L. Summar, M.D., director of the Rare Disease Institute at Children’s National. “This can substantially accelerate the time to diagnosis by providing a robust indicator for patients that need further workup. This first step is often the greatest barrier to moving towards a diagnosis. Once a patient is in the workup system, then the likelihood of diagnosis (by many means) is significantly increased.”

Every year, millions of children are born with genetic disorders — including Down syndrome, a condition in which a child is born with an extra copy of their 21st chromosome causing developmental delays and disabilities, Williams-Beuren syndrome, a rare multisystem condition caused by a submicroscopic deletion from a region of chromosome 7, and Noonan syndrome, a genetic disorder caused by a faulty gene that prevents normal development in various parts of the body.

Most children with genetic syndromes live in regions with limited resources and access to genetic services. The genetic screening may come with a hefty price tag. There are also insufficient specialists to help identify genetic syndromes early in life when preventive care can save lives, especially in areas of low income, limited resources and isolated communities.

“The presented technology can assist pediatricians, neonatologists and family physicians in the routine or remote evaluation of pediatric patients, especially in areas with limited access to specialized care,” said Porras et al. “Our technology may be a step forward for the democratization of health resources for genetic screening.”

The researchers trained the technology using 2,800 retrospective facial photographs of children, with or without a genetic syndrome, from 28 countries, such as Argentina, Australia, Brazil, China, France, Morocco, Nigeria, Paraguay, Thailand and the U.S. The deep learning architecture was designed to account for the normal variations in the face appearance among populations from diverse demographic groups.

“Facial appearance is influenced by the race and ethnicity of the patients. The large variety of conditions and the diversity of populations are impacting the early identification of these conditions due to the lack of data that can serve as a point of reference,” said Linguraru. “Racial and ethnic disparities still exist in genetic syndrome survival even in some of the most common and best-studied conditions.”

Like all machine learning tools, they are trained with the available dataset. The researchers expect that as more data from underrepresented groups becomes available, they will adapt the model to localize phenotypical variations within more specific demographic groups.

In addition to being an accessible tool that could be used in telehealth services to assess genetic risk, there are other potentials for this technology.

“I am also excited about the potential of the technology in newborn screening,” said Linguraru. “There are approximately 140 million newborns every year worldwide of which eight million are born with a serious birth defect of genetic or partially genetic origin, many of which are discovered late.”

Children’s National as well recently announced that it has entered into a licensing agreement with MGeneRx Inc. for its patented pediatric medical device technology. MGeneRx is a spinoff from BreakThrough BioAssets LLC, a life sciences technology operating company focused on accelerating and commercializing new innovations, such as this technology, with an emphasis on positive social impact.

“The social impact of this technology cannot be underestimated,” said Nasser Hassan, acting chief executive officer of MGeneRx Inc. “We are excited about this licensing agreement with Children’s National Hospital and the opportunity to enhance this technology and expand its application to populations where precision medicine and the earliest possible interventions are sorely needed in order to save and improve children’s lives.”

Could whole-exome sequencing become a standard part of state newborn screening?

smiling baby boy

There are concerns about implementing whole-exome sequencing since it takes away the child’s right to decide if they want to know — or not — about their specific inherited disease.

It is still premature to standardize an innovative methodology known as whole-exome sequencing (WES) as part of state newborn screening programs, argues Beth A. Tarini, M.D., M.S., associate director for the Center of Translational Research at Children’s National Hospital, in a new editorial published in JAMA Pediatrics.

About 4 million infants are born annually in the United States. Newborn screening is a mandatory state-run public health program that screens infants for inherited diseases in the first days of life so they can receive treatment before irreversible damage occurs. Several of these screening tests are done on blood drawn from an infant’s heel.

WES holds the potential to screen infants for thousands of disorders and traits, including those that appear in adulthood. But there are concerns about implementing WES since it takes away the child’s right to decide if they want to know — or not — about their specific inherited disease. There is also the unknown effect that it could have on their ability to obtain health insurance.

“As caretakers for their children, parents have the challenge of deciding what kind of information, including genetic, will be valuable for their child,” says Dr. Tarini. “As a society, we have the responsibility of deciding where the healthcare dollars get the best return – especially when it comes to children. We need to start that conversation for universal genomic sequencing of newborns sooner rather than later.”

The Pereira et al. study, appearing in the new edition of JAMA Pediatrics and referenced in Dr. Tarini’s editorial, is the first to demonstrate no significant harm in the initial 10 months of life after performing WES under the best conditions of access to resources and a controlled environment.

While the Pereira et al. study has limited data on the effects of WES on families from underrepresented backgrounds, Dr. Tarini notes that it does provide a critical first step in this area of pediatric genomic research and for policy decision-making about the widespread implementation of WES in newborns.

“Moving forward, the U.S. will have to make a collective decision about the value of WES for newborns,” says Dr. Tarini. That value calculus cannot be made without consideration of the general state of healthcare for infants. As she points out, “This is not an easy question to answer in a country whose infant mortality ranks 34th according to the Organization for Economic Co-operation and Development (OECD).”

Dr. Tarini’s research identifies ways to optimize the delivery of genetic services to families and children, particularly newborn screening. She has also chaired state newborn screening committees and served on several federal newborn screening committees.

coronavirus

Children’s National Hospital and NIAID launch large study on long-term impacts of COVID-19 and MIS-C on kids

coronavirus

Up to 2,000 children and young adults will be enrolled in a study from Children’s National Hospital in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) that will examine the long-term effects of COVID-19 and multisystem inflammatory syndrome in children (MIS-C) after these patients have recovered from a COVID-19 infection.

This $40 million multi-year study will provide important information about quality of life and social impact, in addition to a better understanding of the long-term physical impact of the virus, including effects on the heart and lung. The researchers hope to detail the role of genetics and the immune response to COVID-19, so-called “long COVID” and MIS-C, including the duration of immune responses from SARS-CoV-2, the virus that causes COVID-19. It is fully funded by a subcontract with the NIH-funded Frederick National Laboratory for Cancer Research operated by Leidos Biomedical Research, Inc.

“We don’t know the unique long-term impact of COVID-19 or MIS-C on children so this study will provide us with a critical missing piece of the puzzle,” says Roberta DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases at Children’s National and lead researcher for this study. “I am hopeful that the insights from this enormous effort will help us improve treatment of both COVID-19 and MIS-C in the pediatric population both nationally and around the world.”

Over the past year, more than 3.6 million children have tested positive for SARS-CoV-2 and over 2,800 cases of MIS-C have been reported throughout the U.S. While the vast majority of children with primary SARS-CoV-2 infection may have mild or no symptoms, some develop severe illness and may require hospitalization, including life support measures. In rare cases, some children who have previously been infected or exposed to someone with SARS-CoV-2 have developed MIS-C, a serious condition that may be associated with the virus. MIS-C symptoms can include fever, abdominal pain, bloodshot eyes, trouble breathing, rash, vomiting, diarrhea and neck pain, and can progress to shock with low blood pressure and insufficient cardiac function. Long COVID is a wide range of symptoms that can last or appear weeks or even months after being infected with the virus that causes COVID-19.

The study is designed to enroll at least 1,000 children and young adults under 21 years of age who have a confirmed history of symptomatic or asymptomatic SARS-CoV-2 infection or MIS-C. Participants who enroll within 12 weeks of an acute infection will attend study visits every three months for the first six months and then every six months for three years. Participants who enroll more than 12 weeks after acute infection will attend study visits every six months for three years. The study will also enroll up to 1,000 household contacts to serve as a control group, and up to 2,000 parents or guardians (one parent per participant) will complete targeted questionnaires.

“The large number of patients who will be enrolled in this study should provide us with a truly comprehensive understanding of how the virus may continue to impact some patients long after the infection has subsided,” says Dr. DeBiasi.

The study primarily aims to determine incidence and prevalence of, and risk factors for, certain long-term medical conditions among children who have MIS-C or a previous SARS-CoV-2 infection. The study will also evaluate the health-related quality of life and social impacts for participants and establish a biorepository that can be used to study the roles of host genetics, immune response and other possible factors influencing long-term outcomes.

Children’s National was one of the first U.S. institutions to report that children can become very ill from SARS-CoV-2 infection, despite early reports that children were not seriously impacted. In studies published in the Journal of Pediatrics in May of 2020 and June of 2021, Children’s National researchers found that about 25% of symptomatic COVID patients who sought care at our institution required hospitalization. Of those hospitalized, about 25% required life support measures, and the remaining 75% required standard hospitalization. Of patients with MIS-C, 52% were critically ill.

Study sites include Children’s National Hospital inpatient and outpatient clinics in the Washington, D.C. area, and the NIH Clinical Center in Bethesda, Maryland.

Those interested in participating should submit this form. You will then be contacted by a study team member to review the study details and determine whether you are eligible to participate.

You can find more information about the study here.

Dr. Eric Vilain and researcher in a lab

Children’s National Hospital joins the Mendelian Genomics Research Consortium, receiving $12.8 million

Dr. Eric Vilain and researcher in a lab

Dr. Eric Vilain accompanied by a fellow researcher at the new Research & Innovation Campus.

Children’s National Hospital announces a $12.8 million award from the National Institutes of Health’s National Human Genome Research Institute (NHGRI) to establish the only Pediatric Mendelian Genomics Research Center (PMGRC) as part of a new Mendelian Genomics Research Consortium. Researchers at Children’s National and Invitae — a leading medical genetics company — will identify novel causes of rare inherited diseases, investigate the mechanisms of undiagnosed conditions, enhance data sharing, and generally interrogate Mendelian phenotypes, which are conditions that run in families.

“Our overall approach provides an efficient and direct path for pediatric patients affected with undiagnosed inherited conditions through a combination of innovative approaches, allowing individuals, families and health care providers to improve the management of the disease,” says Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research at Children’s National.

To accelerate gene discovery for Mendelian phenotypes and the clinical implementation of diagnosis, the consortium will leverage the broad pediatric clinical and research expertise of the Children’s National Research Institute and laboratories in partnership with Invitae. The Molecular Diagnostics Laboratory at Children’s National will provide genetic testing for patients in the Washington, D.C., metropolitan area. Invitae will provide genetic testing for patients from elsewhere in the U.S., giving the project a national reach and allowing researchers to leverage more robust data. Integrative analyses will be performed jointly with scientists at Children’s National and Invitae.

“Some patients have genetic test results that are ‘negative,’ meaning the results do not explain their condition. When a patient receives a negative result, it is challenging for parents and doctors to know what to do next,” says Meghan Delaney, D.O., M.P.H., chief of the Division of Pathology and Laboratory Medicine and Molecular Diagnostics Laboratory at Children’s National. “The project will provide an avenue to possibly find an explanation of their child’s condition. Besides filling an important clinical gap, the results will add new knowledge for future patients and the scientific community.”

“Too often parents of children suffering from a rare condition find themselves in a protracted diagnostic odyssey when early intervention could mean better overall outcomes,” says Robert Nussbaum, M.D., chief medical officer of Invitae. “We are proud to partner with Children’s National Research Institute on this important effort to identify the genetic cause of these rare conditions earlier and improve the chances that children with such conditions can receive the appropriate treatments and live healthier lives.”

Deciphering Mendelian conditions will help diagnose more of the estimated 7,000 rare inherited diseases and predict the tremendous variability of clinical presentations in both rare and common conditions caused by the same gene.

There is also a need to establish a new standard of care to bridge the gap in the use of genomic information from diagnosis to improved outcomes. The consortium will establish best practices for obtaining a genetic diagnosis, offering an explanation for the condition to affected patients, and is likely to provide additional explanations for basic biological mechanisms, increasing the knowledge of physiopathology and possibly leading to better condition management.

The PMGRC will enroll an average of 2,600 participants per year with suspected Mendelian phenotypes and previously non-diagnostic tests and their family members. The integration of multiple genomic technologies, including short and long read genome sequencing, optical genome mapping and RNA-sequencing, will enable these discoveries. To disambiguate uncertain variants and candidate genes, the PMGRC will use whole transcriptome analysis, RNA-sequencing, CRE-sequencing and functional modeling.

Since many Mendelian conditions first appear prenatally or during infancy, Children’s National will have a unique bed-to-bench-to-bed symbiosis. Patients eligible for the study will come from across the multiple specialty divisions of Children’s National, including the Children’s National Rare Disease Institute, and nationally through the partnership with Invitae. From there, experts from the Children’s National Center for Genetic Medicine Research will enroll patients and integrate the initial clinical test results with broad-based genomic interrogation, leading to new diagnoses and novel discoveries. Finally, the results will be verified and returned to clinicians, which will help inform targeted therapies.

Typically, the patients eligible for this study jump from specialist to specialist without an answer, have a condition that appears in other family members or they have symptoms involving more than one affected organ, which suggests a complex developmental condition. The PMGRC at Children’s National will help find answers to the causes of many puzzling pediatric conditions, providing faster clinical diagnoses and opening up pathways to potentially better treatments.

Dr. Vilain’s work will be based at the Children’s National Research & Innovation Campus on the grounds of the former Walter Reed Army Medical Center in Washington, D.C. The campus is also home to the Children’s National Rare Disease institute — one of the largest clinical genetics program in the United State that provides care to more than 8,500 rare disease patients.

facial recognition of noonan syndrome

Commercialization of novel facial analysis technology can improve diagnosis of rare disorders in pediatric patients

facial recognition of noonan syndrome

Children’s National Hospital has entered into a licensing agreement with MGeneRx Inc. for its patented pediatric medical device technology using objective digital biometric analysis software for the early and non-invasive screening of dysmorphic genetic diseases such as Noonan syndrome.

Children’s National Hospital has entered into a licensing agreement with life sciences technology company MGeneRx Inc. for its patented pediatric medical device technology using objective digital biometric analysis software for the early and non-invasive screening of dysmorphic genetic diseases. The technology, developed by a multidisciplinary Children’s National team led by Marius George Linguraru, D.Phil, M.A., M.Sc., of the Sheikh Zayed Institute for Pediatric Surgical Innovation and Marshall Summar, M.D., director of the Children’s National Rare Disease Institute (CNRDI), can provide a more advanced diagnostic tool for regions of the world with limited access to geneticists or genetic testing.

The application utilizes artificial intelligence (AI) and machine learning to analyze biometric data and identify facial markers that are indicative of genetic disorders. Physicians can capture biometric data points of a child’s face in real time within the platform, where it scans facial biometric features to determine the potential presence of a genetic disease, which can often be life-threatening without early intervention. Research studies conducted in conjunction with the National Human Genome Research Institute at the National Institutes of Health further enhanced the development of the application in recent years, showing the potential to detect, with a 90 percent accuracy, early diagnosis of 128 genetic diseases across pediatric subjects in 28 countries. These diseases include DiGeorge syndrome (22q11.2 deletion syndrome), Down syndrome, Noonan syndrome and Williams-Beuren syndrome.

“We are delighted to enter into this licensing agreement through Innovation Ventures, the commercialization arm of Children’s National Hospital, which seeks to move inventions and discoveries from Children’s National to the marketplace to benefit the health and well-being of children. Our mission is to add the ‘D’ in development to the ‘R’ in research to accelerate the commercialization of our intellectual property,” says Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National and managing director of Innovation Ventures. “It is through partnerships with startups and the industry that we can achieve this goal and thus we highly value this new partnership with MGeneRx Inc. The acceleration and commercialization of this objective digital biometric analysis technology will not only help diagnose rare genetic disorders – it will also allow for earlier interventions that improve the quality of life for the children living with these conditions.”

Eskandanian adds that the social impact of this technology is especially profound in lower income nations around the world, where there is a high prevalence of rare genetic conditions but a severe lack in the specialty care required to diagnose and treat them. Additional data collected through the expanded use of the technology will help to further develop the application and expand its capabilities to identify and diagnose additional rare genetic conditions.

The licensing agreement was arranged by the Children’s National Office of Innovation Ventures, which is focused on the commercialization of impactful new pediatric medical device technologies and therapies to advance children’s health care. Created to catalyze the ongoing translational research of the Children’s National Research Institute (CNRI) as well as inventions by hospital’s clinicians, Innovation Ventures focuses on four core pillars to advance pediatric medical technologies including a Biodesign program, partnerships and alliances to augment internal capacity, seed funding to de-risk technologies and validate market and clinical relevance, and back-office operations to manage intellectual property and licensing activities. Since 2017, Children’s National intellectual property has served as the basis for over 15 licensing or option agreements with commercial partners.

Providing access to an array of experts and resources for pediatric innovators is one of the aims of the Children’s National Research & Innovation Campus, a first-of-its-kind focused on pediatric health care innovation, with the first phase currently open on the former Walter Reed Army Medical Center campus in Washington, D.C. With its proximity to federal research institutions and agencies, universities, academic research centers, as well as on-site incubator Johnson and Johnson Innovation – JLABS, the campus provides a rich ecosystem of public and private partners, which will help bolster pediatric innovation and commercialization.

little boy at doctor

Demographic, clinical and biomarker features of MIS-C

little boy at doctor

In a new observational study, researchers provide insight into key features distinguishing MIS-C patients to provide a more realistic picture of the burden of disease in the pediatric population and aid with the early detection of disease and treatment for optimal outcomes.

Multisystem Inflammatory Syndrome in Children (MIS-C) significantly affected more Black and Latino children than white children, with Black children at the highest risk, according to a new observational study of 124 pediatric patients treated at Children’s National Hospital in Washington, D.C. Researchers also found cardiac complications, including systolic myocardial dysfunction and valvular regurgitation, were more common in MIS-C patients who were critically ill. Of the 124 patients, 63 were ultimately diagnosed with MIS-C and were compared with 61 patients deemed controls who presented with similar symptoms but ultimately had an alternative diagnosis.

In the study, published in The Journal of Pediatrics, researchers provide insight into key features distinguishing MIS-C patients to provide a more realistic picture of the burden of disease in the pediatric population and aid with the early detection of disease and treatment for optimal outcomes. The COVID-linked syndrome has affected nearly 4,000 children in the United States in the past year. Early reports showed severe illness, substantial variation in treatment and mortality associated with MIS-C. However, this study demonstrated that with early recognition and standardized treatment, short-term mortality can be nearly eliminated.

“Data like this will be critical for the development of clinical trials around the long-term implications of MIS-C,” says Dr. Roberta DeBiasi, M.D., lead author and chief of the Division of Pediatric Infectious Diseases at Children’s National. “Our study sheds light on the demographic, clinical and biomarker features of this disease, as well as viral load and viral sequencing.”

Of the 63 children with MIS-C, 52% were critically ill, and additional subtypes of MIS-C were identified including those with and without still detectable virus, those with and without features meeting criteria for Kawasaki Disease, and those with and without detectable cardiac abnormalities. While median age (7.25 years) and sex were similar between the MIS-C cohort and control group, Black (46%) and Latino (35%) children were overrepresented in the MIS-C group, especially those who required critical care. Heart complications were also more frequent in children who became critically ill with MIS-C (55% vs. 28%). Findings also showed MIS-C patients demonstrated a distinct cytokine signature, with significantly higher levels of certain cytokines than those of controls. This may help in the understanding of what drives the disease and which potential treatments may be most effective.

In reviewing viral load and antibody biomarkers, researchers found MIS-C cases with detectable virus had a lower viral load than in primary SARS-CoV-2 infection cases, but similar to MIS-C controls who had alternative diagnoses, but who also had detectable virus. A larger proportion of patients with MIS-C had detectable SARS-CoV-2 antibodies than controls. This is consistent with current thinking that MIS-C occurs a few weeks after a primary COVID-19 infection as part of an overzealous immune response.

Viral sequencing was also performed in the MIS-C cohort and compared to cases of primary COVID-19 infection in the Children’s National geographic population. 88% of the samples analyzed fell into the GH clade consistent with the high frequency of the GH clade circulating earlier in the pandemic in the U.S. and Canada, and first observed in France.

“The fact that there were no notable sequencing differences between our MIS-C and primary COVID cohorts suggests that variations in host genetics and/or immune response are more likely primary determinants of how MIS-C presents itself, rather than virus-specific factors,” says Dr. DeBiasi. “As we’ve seen new variants continue to emerge, it will be important to study their effect on the frequency and severity of MIS-C.”

Researchers are still looking for consensus on the most efficacious treatments for MIS-C. In a recent editorial in the New England Journal of Medicine, Dr. DeBiasi calls for well-characterized large prospective cohort studies at single centers, and systematic and long-term follow-up for cardiac and non-cardiac outcomes in children with MIS-C. Data from these studies will be a crucial determinant of the best set of treatment guidelines for immunotherapies to treat MIS-C.

US News badges

For fifth year in a row, Children’s National Hospital nationally ranked a top 10 children’s hospital

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll list, which ranks the top 10 children’s hospitals nationwide. In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fifth year in a row.

For the eleventh straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“It is always spectacular to be named one of the nation’s best children’s hospitals, but this year more than ever,” says Kurt Newman, M.D., president and CEO of Children’s National. “Every member of our organization helped us achieve this level of excellence, and they did it while sacrificing so much in order to help our country respond to and recover from the COVID-19 pandemic.”

“When choosing a hospital for a sick child, many parents want specialized expertise, convenience and caring medical professionals,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings have always highlighted hospitals that excel in specialized care. As the pandemic continues to affect travel, finding high-quality care close to home has never been more important.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

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.

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

The other three specialties ranked among the top 50 were cardiology and heart surgerygastroenterology and gastro-intestinal surgery, and urology.

Francis Collins

Francis S. Collins, M.D., Ph.D. from NIH: The future of genomic medicine and research funding opportunities

Kurt Newman and Francis Collins

Genomic medicine, diversity, equity and inclusion (DEI), a world post-COVID-19 and pediatric research funding were among the topics discussed during the “Special Fireside Chat” keynote lecture at the 2021 Children’s National Hospital Research, Education and Innovation Week.

Francis S. Collins, M.D., Ph.D., director at the National Institutes of Health (NIH), is well known for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book.

The President and CEO of Children’s National, Kurt Newman, M.D., joined Dr. Collins during the “Special Fireside Chat” keynote lecture. Dr. Newman posed several health care-related questions to Dr. Collins over the course of 30 minutes. Dr. Collins’s responses shed light on what it takes to advance various research fields focused on improving child health and develop frameworks that advocate for DEI in order to foster a more just society.

Q: You have been involved with genomic medicine since its inception. You discovered the gene causing cystic fibrosis and led the Human Genome project. What do you see as the future of genomic medicine, especially as it relates to improving child health?

A: Thank you for the question, Kurt. First, I wanted to say congratulations on your 150th anniversary. Children’s National Hospital has been such a critical component for pediatric research and care in the Washington, D.C., area, and at the national and international levels. We at the NIH consider it a great privilege to be your partner in many of the things that we can and are doing together.

Genomic medicine has certainly come a long way. The word genomics was invented in 1980, so we have not been at this for that long. Yet, the success of the Human Genome Project and the access to cost-effective tools for rapid DNA sequencing have made many things possible. It took a lot of effort, time and money to discover the gene that causes cystic fibrosis. Kurt, if you look at what we did, while it was rewarding, it was a challenging problem that occupied the hearts of the scientific community in 1980. Now, a graduate student at Children’s National that has access to DNA samples, a thermal cycler, a DNA sequencer and the internet could do in about a week what it took us a decade and with 50 people.

We have been able to rocket forward as far as identifying the genetic causes of 6,500 diseases, where we know precisely the molecular glitch responsible for those conditions. While most of those are rare diseases, it leads to the opportunity for immediate diagnosis, which used to be a long and troubled journey.

DNA sequencing has increasingly become an essential tool in newborns, especially when trying to sort out puzzling diagnosis for specific syndromes or phenotypes that are not immediately clear. Additionally, DNA sequencing significantly impacted clinical care in cancer because it made it possible to look at the mutations driving the malignancy and its genetic information that can lead to interventions. This approach is going forward in the next few years in ways that we can see now. Although I am a little reluctant to make predictions because I have to be careful about that, it may be possible to obtain complete genome sequences that can be yours for life and place them into the medical record to make predictions about future risks and choices about appropriate drugs. This path costs less than any imaging tests.

Q: The racial justice movement that was brought back to the forefront this past year has, once again, reaffirmed that this country has so much more work to do in order to end systemic racism. You have been at the forefront of promoting diversity, equity and inclusion in research and at the NIH. What do you and the NIH plan to do further DEI efforts in research and in general so that we can be a more just and equitable society?

A: I appreciate you raising this, Kurt. Diversity, equity and inclusion (DEI) is an issue where everyone should be spending a lot of time, energy and passion. You are right. 2020 will be remembered for COVID-19. I also think it will be remembered for the things that occurred around the killing of George Floyd, and the recognition of the very foundation that is still infected by this terribly difficult circumstance of structural racism. I convened a group of about 75 deep thinkers about these issues, many of them are people of color from across the NIH’s different areas of activities. I asked the group to come forward with a bold set of proposals. This effort is how the program UNITE came together to work hard on this, which is now making recommendations that I intend to follow. We are determined to close that gap and pursue additional programs that will allow us to be more successful in recruiting and retaining minority groups, for example. We need to do something with our health disparity and research portfolio as well to ensure that we are not just looking around the edges of the causes for racial inequities. We are digging deeper into what the structural racism underpinnings are and what we can do about it. I am particularly interested in supporting research projects that test intervention and not just catalog the factors involved. We have been, at times, accused and maybe rightly so of being more academic about this, and, less kindly, we have been accused of admiring the problem of health disparities as opposed to acting on it. We are ready to act.

Q: COVID has affected us all in so many ways. Could you tell us what this past year has been like for you? Also, how is the NIH preparing for a soon-to-be post-COVID pandemic?

A: This is the time to contemplate the lessons learned as everyone knows that the last worst pandemic happened over a century ago. One thing that maybe will vex us going forward, which we already started to invest in a big way, is this whole long COVID syndrome, also referred to post-acute sequelae, to understand precisely the consequences and mechanisms like Multisystem Inflammatory Syndrome in Children (MIS-C). Before moving to the next pandemic, we must think about how we will help understand those who suffer from long COVID syndrome. As far as the broader lessons learn, Kurt, we must expect that there will be other pandemics because humans are interacting more with animals, so zoonosis is likely to emerge. We need to have a clear sense of preparation for the next one. For instance, we are working on this right now, but we need to have a stronger effort to develop small molecules of anti-viral drugs aimed at the major viral classes, so we do not have to start from scratch. We also need clinical trial networks warm all the time, ready to go and to learn how valuable public partnerships can be to get things done in a hurry.

Editor’s Note: The responses in this Q+A have been modified to fit the word count.

Andrea Hahn

Pediatric Research names Andrea Hahn, M.D., M.S., early career investigator

Andrea Hahn

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

For her work on the impact of bacterial functional and metabolic activity on acute episodes of cystic fibrosis, the journal Pediatric Research recognized Andrea Hahn, M.D., M.S., as Pediatric Research’s Early Career Investigator.

Cystic fibrosis is an autosomal recessive genetic disease, affecting more than 70,000 people worldwide. The condition’s morbidity and mortality are recurrent and result in a progressive decline of lung function.

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

The exact mechanisms of the bacteria that chronically infect the airway triggering acute cystic fibrosis episodes, also known as pulmonary exacerbations, remain unclear. Dr. Hahn’s research is one of the few to explore this gap and found an association with long-chain fatty acid production in cystic fibrosis inflammation.

“As a physician-scientist, there are many competing priorities between developing and executing good science — including writing manuscripts and grants — and providing excellent patient care both directly and through hospital-wide quality improvement initiatives,” said Dr. Hahn. “It is often easier to have successes and feel both effective and appreciated on the clinical side. This recognition of my scientific contributions to the medical community is motivating me to continue pushing forward despite the setbacks that often come up on the research side.”

The exposure to many programs and institutions gave Dr. Hahn the foundation to create a research program at Children’s National that helps decipher the complexities of antibiotic treatment and how it changes the airway microbiome of people with cystic fibrosis. The program also explores the impacts of antibiotic resistance and beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) — the oldest class of antibiotics used to treat infections.

Dr. Hahn believes that the people and environment at Children’s National Hospital allowed her to grow and thrive as a physician-scientist.

“I was initially funded through an internal K12 mechanism, which was followed up by Foundation support, which was only possible because of the strong mentorship teams I have been able to build here at Children’s National,” said Dr. Hahn. “My division chief has also been very supportive, providing me with both protected time as well as additional resources to build my research lab.”

She is particularly appreciative of Robert Freishtat, M.D., M.P.H, senior investigator at the Center for Genetic Medicine Research, and Mary Callaghan Rose (1943-2016).

“Robert Freishtat has been a great advocate for me, and I am indebted to him for my success thus far in my career,” said Dr. Hahn. “Likewise, I want to specifically recognize Mary Rose. She was a great scientist at Children’s National until her death in 2016. She gave me the initial opportunity and support to begin a career studying cystic fibrosis, and she is missed dearly.”

You can learn more about Dr. Hahn’s research in this Pediatric Research article.

Injury triggered change in ER calcium of a muscle cell

ER maintains ion balance needed for muscle repair

Injury triggered change in ER calcium of a muscle cell

A new study led by Jyoti Jaiswal, M.Sc., Ph.D., principal investigator at Children’s National Hospital, identifies that an essential requirement for the repair of injured cells is to cope with the extracellular calcium influx caused by injury to the cell’s membrane. Credit: Goutam Chandra, Ph.D.

Physical activity can injure our muscle cells, so their ability to efficiently repair is crucial for maintaining muscle health. Understanding how healthy muscle cells respond to injury is required to understand and treat diseases caused by poor muscle cell repair.

A new study led by Jyoti Jaiswal, M.Sc., Ph.D., principal investigator at Children’s National Hospital, identifies that an essential requirement for the repair of injured cells is to cope with the extracellular calcium influx caused by injury to the cell’s membrane.

This study, published in the Journal of Cell Biology, identifies endoplasmic reticulum (ER) – a network of membranous tubules in the cell – as the site where the calcium entering the injured cell is sequestered. Using limb girdle muscular dystrophy 2L (LGMD2L) patient cells and a model for this genetic disease, the study shows impaired ability of diseased muscle cells to cope with this calcium excess. It also shows that a drug to sequester excess calcium counters this ion imbalance and reverses the diseased cell’s repair deficit.

“The study provides a novel insight into how injured cells in our body cope with calcium ion imbalance during injury,” Dr. Jaiswal explained. “This work also addresses how calcium homeostasis is compromised by a genetic defect that leads to LGMD2L. It also offers a proof of principle approach to restore calcium homeostasis, paving the path for future work to develop therapies targeting this disease.”

According to Dr. Jaiswal, this work also addresses the current lack of understanding of the basis for exercise intolerance and other symptoms faced by LGMD2L patients.

“This study opens the path for developing targeted therapies for LGMD2L and provides a fundamental cellular insight into a process crucial for cell survival,” said Goutam Chandra, Ph.D., research fellow and lead author of this study.

The Center for Genetic Medicine Research at Children’s National is among only a handful across the world to study this rare disease. These findings are unprecedented in providing the mechanistic insights needed to develop treatment for it.

In addition to Dr. Jaiswal and Chandra, the study co-authors include Sreetama Sen Chandra, Ph.D., Davi Mazala, Ph.D., and Jack VanderMeulen, Ph.D., from Children’s National, and Karine Charton, Ph.D., and Isabelle Richard, Ph.D., from Université Paris-Saclay.

Research & Innovation Campus

A unified vision for children’s health

Research & Innovation Campus

The nation’s first research and innovation campus focused on children’s health is in the midst of a phased opening. Deemed a one-of-a-kind endeavor to transform pediatric research and health care, the Children’s National Research & Innovation Campus in Washington, D.C., has been years in the making.

How Children’s National Hospital, Virginia Tech, Johnson & Johnson Innovation – JLABS are creating a pediatric and healthcare research hub in Washington, D.C.

The nation’s first research and innovation campus focused on children’s health is in the midst of a phased opening. Deemed a one-of-a-kind endeavor to transform pediatric research and health care, the Children’s National Research & Innovation Campus in Washington, D.C., has been years in the making.

Leaders from Children’s National Hospital, Virginia Tech and Johnson & Johnson Innovation – JLABS detailed how unprecedented partnerships and a shared vision for the future were key to turning a decade-old dream into a reality during a panel discussion on February 24, 2021, at the Healthcare Project Delivery Conference. The virtual meeting brought together more than 150 senior hospital administrators from more than 60 hospitals and health systems, as well as healthcare facility management professionals, healthcare construction leaders, designers and architects.

“The idea for the campus started with an impressive, unique vision to create a pediatric research and innovation ecosystem where we could work alongside best-in-class research partners like Virginia Tech and Johnson & Johnson Innovation to advance discovery, while also allowing Children’s National to expand clinically on the main campus,” said Children’s National president and chief executive officer, Kurt Newman, M.D.. “It is our collective hope that the campus will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.”

The research partnership with Children’s National strategically triangulates the Virginia Tech’s billion-dollar investments in Southwest Virginia, the emerging Virginia Tech Innovation Campus in Alexandria and now the Children’s National Research & Innovation Campus in Washington, D.C.

“Fusing together strengths in cancer research, neuroscience, and computer engineering gives Virginia Tech a great opportunity to grow its physical presence in the D.C. area with a holistic purpose,” said Michael Friedlander, Ph.D., Virginia Tech’s vice president for health sciences and technology, and the Fralin Biomedical Research Institute at VTC’s executive director.

Friedlander has worked with Children’s National’s leadership for more than 25 years, and played a pivotal role in establishing the university’s footing on the Washington, D.C., campus.

Together Virginia Tech and Children’s National have launched an annual collaborative brain cancer pilot research program between the two institutions, as well as joint recruitment efforts for the first wave of Fralin Biomedical Research Institute faculty members to work in the campus’s state-of-the-art laboratories.

The 12-acre Children’s National Research & Innovation Campus, part of a 70-acre development that was formerly the Walter Reed Army Medical Center, will also become a hub for commercial innovation. In 2019, Johnson & Johnson Innovation and Children’s National collaboratively announced plans to launch JLABS @ Washington, DC, which aims to strengthen and expand the region’s network to attract the full breadth of science and technology innovators who are focused on developing transformative solutions to improve patients’ and consumers’ lives. The 32,000-square-foot life science incubator will house up to 50 start-up companies from across the pharmaceutical, medical device, consumer, and health technology sectors.

Researchers at Children’s National and Virginia Tech alike will benefit from the opportunity to collaborate with entrepreneurs working at the incubator to commercialize discoveries made in the lab.

“What an incredible opportunity for our researchers who are committed to bringing discoveries out of the lab to benefit the public,” Friedlander said. “These partnerships have established a special opportunity that aligns very well with the university’s strategic plan to grow in health sciences innovation and commercialization.”

Newman and Sally Allain, head of JLABS @ Washington, DC, both commented on how important it was to have an academic partner of Virginia Tech’s stature as one of the new enterprise’s anchoring tenants.

Recruitment for the first wave of Virginia Tech researchers to work on the new campus has just begun. Construction is anticipated to be completed by summer, 2021.

Gracie Popielarcheck

Raising awareness about Turner Syndrome

Gracie Popielarcheck

Gracie Popielarcheck was diagnosed at age one with Turner Syndrome.

By Roopa Kanakatti Shankar, M.D., M.S., Director of the Turner Syndrome Program at Children’s National Hospital.

The Children’s National  Turner Syndrome Clinic is part of the Division of Endocrinology and Diabetes which is ranked by U.S. News & World Report as one of the top 10 programs in the nation. The clinic opened in January 2019 and is the first of its kind in the Washington, D.C., region. A multidisciplinary clinic is held once a month with a team experts in cardiology, endocrinology, psychology, gynecology and genetics to help care for the needs of patients with Turner Syndrome all in one day. The referral network of specialties includes neuropsychology, otolaryngology, audiology, orthopedics, urology and dentistry.

Turner syndrome (TS) is a rare disease affecting girls, with a prevalence of around 25-50 out of every 100,000 females. It is caused by partial or complete loss of the second sex chromosome. This affects multiple organs and can cause heart defects, skeletal abnormalities, hearing loss and learning difficulties. It also affects growth and puberty and can cause infertility. Although the condition was first described in 1938 by Henry Turner, an endocrinologist from Oklahoma, and is well characterized, there is a significant delay in diagnosis and recognition of the condition, especially in milder forms that can still significantly impact the well-being of the individual.

Gracie Popielarcheck with a pet bird

“Having a Turner Syndrome clinic near our city has made life so much easier,” says Gracie’s mom, Leslie Popielarcheck. “We can see all of Gracie’s specialists all in one day and under one roof.”

Families often ask why it took so long to recognize this condition. Many findings can be subtle, the presentation can vary greatly and often short stature may be overlooked in some girls. We now recognize that the classic form (monosomy X) impacts less than half of the girls and the rest have mosaicism (45,X/ 46XX) or other structural abnormalities in the X-chromosome. Recognizing features beyond the classic “short stature, neck webbing, lymphedema and cardiac defects” is indeed important to get timely care for these girls and women across the lifespan. Many have recurrent ear infections and hearing loss. Most have a normal intelligence, and even superior verbal skills but face challenges in visual spatial perception, executive function, working memory and social cognition that impact academic achievement.

13-year-old Gracie Popielarcheck was diagnosed with TS at the age of one after her parents noticed a delay in her speech and development. “We had never heard of Turner Syndrome when Gracie was diagnosed,” says Leslie Popielarcheck, Gracie’s mom. “Gracie didn’t have the classic physical features that girls with Turner Syndrome are known to have.”

With support, most of these girls and women can manage the medical and psychosocial challenges and rise to their full potential. Advances in the field and multidisciplinary care models have helped in the establishment of TS clinics across the country that strive to improve the standard care for these girls.

However, several challenges remain:

  • Improving awareness among primary care physicians in regard to the extended spectrum and variability of presentation at a wide variety of ages
  • Decreasing health disparities and making multidisciplinary clinics and comprehensive care available and accessible even to disadvantaged communities
  • Ensuring adequate medical and social support for transition of young adults and care of adults with Turner syndrome
Gracie P., Kyra Dorfman with Dr. Shankar

Kyra Dorfman, Dr. Shankar and Gracie.

Our TS program, initiated 2 years ago, aims to overcome these challenges and provide care to families impacted by TS in our community. We strive to serve as a Regional Resource for the community as well as physicians in our community and have been recognized by the TSGA (Turner syndrome Global Alliance) as one of only nine clinics nationwide with a Level 4 designation.

“Having a Turner Syndrome clinic near our city has made life so much easier,” Popielarcheck says. “We can see all of Gracie’s specialists all in one day and under one roof.”

As we highlight these resources for the Turner Syndrome Awareness Month this February 2021, and celebrate the strength and tenacity of our beautiful girls, we hope our efforts will improve recognition of the condition and delivery of comprehensive medical care and support to the community we serve.

The Children's National Research & Innovation Campus

Children’s National Research & Innovation Campus welcomes Rare Disease Institute as first occupant

The Children's National Research & Innovation Campus

The Rare Disease Institute, which includes the largest clinical group of pediatric geneticists in the nation, focuses on developing the clinical care field of the more than 8,000 rare diseases currently recognized and advancing the best possible treatments for children with these diseases.

The Children’s National Research & Innovation Campus (RIC), the first-of-its-kind pediatric research and innovation hub located in Washington, D.C., now has its first occupant – the Rare Disease Institute (RDI).

The institute, which includes the largest clinical group of pediatric geneticists in the nation, focuses on developing the clinical care field of the more than 8,000 rare diseases currently recognized and advancing the best possible treatments for children with these diseases.

With the advent of advanced DNA sequencing, databanks, informatics, new technology, pediatric consortiums and global partnerships, clinical researchers have never been in a better position to diagnose and treat rare diseases. As this field of medicine continues to rapidly evolve, the benefits provided to patients, families, clinicians and researchers through its new home at the RIC will further accelerate the trajectory of rare disease from an academic specialty into a mainstream medical field.

Marshall Summar, M.D., director of the RDI and chief of the Division of Genetics and Metabolism at Children’s National, is well-known for pioneering work in caring for children diagnosed with rare diseases. He developed and launched the world’s first RDI at Children’s National in 2017, and it became the first Clinical Center of Excellence designated by the National Organization for Rare Diseases (NORD). Dr. Summar discusses how this move will positively impact treatment, services and discovery on a national level.

Q: What are the patient benefits of the move to the RIC?

A: Patients with genetic conditions spend a lot of time visiting the hospital. By creating an easy access environment that is designed around their needs, we can provide world-class care to the families we work with. We designed extensive telemedicine capacity into the clinic so we can continue to expand our digital reach to wider areas. The parking facility is also a huge plus for our families with mobility impairments. The garage is only steps away from the clinic entrance. The architectural team worked closely with the clinical team to create a patient-centric facility for a safe and positive experience.

Q: What are the research benefits of being on the RIC?

A: One of our core goals at the RIC was to create research “neighborhoods.” A focus of the first phase of the RIC occupancy is genetics and the RDI is the clinical manifestation of that focus. Having the clinical service that sees patients with genetic disease, sharing space and campus with the Center for Genetic Medicine Research team and the molecular genetics laboratory creates that thematic neighborhood. Some of the best basic science ideas and projects come from the clinical world. Close interaction between the clinicians and the scientists will enhance those “spark” encounters. In addition, the physicians in the RDI who do bench research are also part of the genetic medicine program which furthers these interactions.

Marshall Summar

Marshall Summar, M.D., director of the RDI and chief of the Division of Genetics and Metabolism at Children’s National.

Q: What would you say has been the most significant change to your field in the past decade?

A: The ability to access next-generation genetic sequencing for more and more of our patients. The percentage of patients who can get a meaningful diagnosis with these technologies increases every year. With these techniques, we are finding new links between genes and disease at the rate of 5-10 per week.

Q: What excites you most about the future of medical genetics and rare diseases?

A: Two things are really exciting to me. The first is the ability to diagnose more patients than at any time in history. The second is the rate at which new genetic/rare disease therapies are being developed (around 50% of the FDA new drug approvals per year).

As the largest clinical program in North America and with our new location on this dedicated research and innovation campus in Washington, D.C., Children’s National and the RDI are uniquely poised to dramatically change the field of rare disease medicine. Our clinical models have started spreading to other centers across the country and will help shape the field for years to come. We are evolving rare disease into a true mainstream medical field, and the ability to make this type of change to a field is very unique to Children’s National.

Learn more about the Children’s National Research & Innovation Campus.

Research & Innovation Campus building entrance

Research campus provides opportunities for entrepreneurs and innovators

Research & Innovation Campus building entrance

Artist’s rendering of the entrance to the research building on the Children’s National Research & Innovation Campus.

In 2021, Children’s National Hospital intends to open a one-of-a-kind pediatric research and innovation hub, located on a portion of the former Walter Reed Army Medical Center campus. Called the Children’s National Research & Innovation Campus, this collection of facilities will house both our Research and Rare Disease Institutes. In the 160,000 square foot space, we are excited to pursue breakthrough potential discoveries that aim to quickly translate into new treatments and technologies benefitting our most vulnerable population, children and babies.

The campus also represents an opportunity for entrepreneurs and innovators who share our passion for finding new and better ways to care for children thanks to a collaboration with Johnson & Johnson Innovation called JLABS @ Washington, DC, a facility within the campus.

Strategically located with proximity to leading academic research institutions, medical schools and federal research institutions and agencies, the JLABS @ Washington, DC site will be open to emerging pharmaceutical, medical device, consumer and health technology companies aiming to advance the development of new drugs, medical devices, precision diagnostics and health technologies, including applications in pediatrics.

Johnson & Johnson Innovation – JLABS, in addition to offering emerging life science companies modular lab units, office space, shared core laboratory equipment and business facilities, aims to link the entrepreneurs within the District and across the greater Virginia and Maryland regions with the full breadth of the Johnson & Johnson Innovation model, including opportunities for collaboration, a resource hub, educational events and mentorship from experts from the Johnson & Johnson Family of Companies. AlgometRx, a spin-off company from Children’s National Hospital, will be among the first residents of JLABS @ Washington, DC, which aims to opens in 2021, as an awardee of the JLABS @ Washington, DC Children’s QuickFire Challenge.

AlgometRx’s novel technology was developed by hospital pain medicine expert Julia Finkel, M.D., The non-invasive handheld device aims to objectively measure pain by capturing real-time images of a patient’s pupillary response and applies proprietary algorithms to determine the patient’s pain type and intensity.

Do you have a pharmaceutical, medical device, consumer health or health technology innovation that could benefit from this unique and transformational ecosystem? If so, we invite you to submit an application to be considered for joining us at JLABS @ Washington, DC. Learn more by visiting the JLABS website.

Lee Beers

Lee Beers, M.D., F.A.A.P, begins term as AAP president

Lee Beers

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
  • Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
  • Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.

Maddox and family

Family love and the right care for neurofibromatosis type 1 give Maddox a fresh start

Maddox and family

Maddox and his family in early 2020.

13-year-old Maddox Gibson is learning to cook. He says he wants to be a chef and wants to make meals for people who need it most — the homeless and the hungry.

It makes sense that he’s eager to help people who need it. As a young child growing up in a group home in his native country of China, he knows firsthand how important that support can be. In 2017 at age 10, he found his own endless supply of love and support when he met and was adopted by the Gibson family.

Zhen Chao, now called Maddox, was born in China with a genetic condition called neurofibromatosis type 1 that can cause painful or disfiguring tumors called plexiform neurofibromas. Zhen Chao had two on his head when he arrived — on his scalp and on his left optic nerve — which had been largely untreated for most of his life in China. On top of that, his right leg had been fractured and not fixed properly years before, causing him pain and weakness that left him wheelchair bound.

Adoptive mom Lindsey, a registered nurse, knew he would need special care to meet all the unique challenges he faced, and she’d done her homework — he needed the expertise of Miriam Bornhorst, M.D.,  and the Gilbert Family Neurofibromatosis Institute at Children’s National Hospital to help him thrive in his new life in the U.S. Since shortly after he came to the U.S., Lindsey has been driving Maddox the 6-plus hours from their home in North Carolina to Washington, D.C., regularly, to get care for all of his health challenges.

Maddox’s optic neurofibroma was too large when he arrived at Children’s National for a simple surgical removal. Due to her role as the lead investigator on a cutting edge clinical trial for the orphan drug selumetinib — a so-called MEK inhibitor that has shown early promise at reducing the cell growth of tumors like plexiform neurofibromas, Dr. Bornhorst enrolled Maddox in a compassionate use program for the drug, an opportunity that is not widely available. The drug was initially developed for something completely different — treatment of melanoma and non-small cell lung cancer in adults–but has been adapted through its FDA orphan drug designation for pediatric clinical trials in NF1. In the time since Maddox started taking it, it was approved for use in NF1 patients by the FDA.

The trial drug did its job — in late 2019, Maddox’s tumor had shrunk enough that chief neurosurgeon Robert Keating, M.D., and plastic surgeon Michael Boyajian, M.D., were able to successfully remove it. Follow-up procedures led by that team have also worked to repair the tissue that was impacted by the optic neurofibroma.

In addition to treatment of his neurofibromas, Maddox and his mom are able to see every service they need during one stay in D.C. The Neurofibromatosis Institute works closely across specialties, so his corrective surgery for his leg from Children’s chief of orthopaedics, Matthew Oetgen, M.D., MBA, in September 2019. He was assessed and prescribed physical therapy early in the process and even before surgery, so now he’s stronger than ever and walking. Learning difficulties, including autism and ADHD are common in NF1 patients, and so the NF Institute’s neuropsychology team has evaluated him and worked with the family to find resources and strategies near home that will support him. It should be noted, those learning difficulties only became apparent after Maddox taught himself English from scratch in only two years’ time with the help of his school’s ESOL program.

This kind of full spectrum care, from clinical assessment to surgical treatment and psychological supports, is crucial to the lives of patients with neurofibromatosis type 1 and is only available at a pediatric specialty care institution like Children’s National. The hospital has gathered some of the preeminent researchers, surgeons, and physicians within the NF Institute to make sure that the care families will travel hundreds of miles to receive is the best possible, using the latest evidence-based treatments for every challenge they face.

Though his care and follow-ups will continue at Children’s National Hospital and his condition may pose  new challenges in the future, for now, Maddox is able to focus on exploring new things and doing what he loves — playing outdoors with his family, learning to cook and building with Legos.

Drs. Dewesh Agrawal, Andrew Dauber, Robert Freishtat, Vittorio Gallo

Four Children’s National Hospital leaders named to APS

Drs. Dewesh Agrawal, Andrew Dauber, Robert Freishtat, Vittorio Gallo

Drs. Dewesh Agrawal, Andrew Dauber, Robert Freishtat and Vittorio Gallo were named as 2021 American Pediatric Society members.

The American Pediatric Society (APS) has announced 55 new members, four of which are experts from Children’s National Hospital. Founded in 1888, the APS is the first and most prestigious academic pediatric organization in North America.

APS members are recognized child health leaders of extraordinary achievement who work together to shape the future of academic pediatrics. New members are nominated by current members through a process that recognizes individuals who have distinguished themselves as child health leaders, teachers, scholars, policymakers and/or clinicians.

“Our members represent the most distinguished and accomplished academic leaders in pediatrics whose outstanding work has advanced child health,” said APS President Steven Abman, M.D. “I am honored to welcome this exceptional group of individuals to the APS. The APS is especially looking forward to the active engagement of our membership with many exciting programs within the organization that are directed towards improvements in academic pediatric medicine, including more vigorous approaches to express our values of anti-racism, equity, diversity and inclusion.”

APS 2021 active new members from Children’s National are:

  • Dewesh Agrawal, M.D., vice-chair for Medical Education at Children’s National. Agrawal’s career has been marked by academic honors and teaching awards at every stage of his training and faculty employment. He has relentlessly devoted his energy to improving the educational experience for students, residents and fellows at Children’s National.
  • Andrew Dauber, M.D., M.M.Sc., chief of Endocrinology at Children’s National. Dr. Dauber’s leadership is reflected, nationally and internationally, in his ability to create research consortia, bringing together investigators to tackle complex questions. For example, he leads an NIH-funded consortium on the genetics of short statures, with multiple top children’s hospitals as partners. He also leads a large clinical trial testing a novel therapeutic agent for genetic short stature.
  • Robert Freishtat, M.D., M.P.H., senior investigator in the Center for Genetic Medicine of the Children’s National Research Institute (CNRI). Dr. Freishtat has authored or co-authored more than 100 articles and book chapters in the fields of pediatric lung injury, asthma, obesity, exosomes and emergency medicine. His research has been continuously funded by the NIH since 2003.
  • Vittorio Gallo, Ph.D., chief research officer at Children’s National and scientific director of CNRI. Dr. Gallo’s scientific success is attested to by over 130 peer-reviewed publications, many in very high-profile journals, as well as over 30 review articles and book chapters. He has received many national and international awards, including the NINDS Javits award in Neuroscience in 2018. Dr. Gallo has served on the editorial boards of many neuroscience journals, including Glia and the Annual Review in Neuroscience, and has been reviewing editor for the Journal of Neuroscience, all of which is a testament to the tremendous impact that his studies have had on the advancement of neurosciences.

“These new members represent multiple areas of Children’s National and have all leveraged the intersection of science, medicine and clinical education to make advances in their field of study,” said Stephen J. Teach, M.D., M.P.H., chair of the Department of Pediatrics at Children’s National. “Their work has, and will continue to, advance pediatric health care, and I congratulate them on their APS membership.”

little girl measuring her height

Study may change treatment of childhood growth disorders

little girl measuring her height

A new Phase 2 study at Children’s National will look at using the drug vosoritide to promote growth in children with growth disorders.

A child’s growth is often measured by pediatricians during routine physicals to identify abnormalities of growth and stature. An abnormality in these measurements could mean a child has a growth disorder. There are many different causes of growth disorders. Some can be the result of defects in genes related to the growth plate, which is the tissue near the end of long bones that grows as the child grows. Children with a growth disorder can present many different symptoms including short stature, joint pain, heart problems, bone problems and developmental delays. Scientists still have a lot to learn about what exactly causes these genetic growth disorders and treatments are limited, especially in the pediatric population. Growth hormone is not uniformly helpful and has only been approved for a small number of conditions.

Vosoritide is an investigational drug that directly targets the growth plate to promote growth. It is an analog of the amino acid C-type natriuretic peptide (CNP). It binds its receptor on healthy cartilage cells called chondrocytes and is currently under investigation in clinical trials as a treatment for the bone growth disorder achondroplasia.

“Vosoritide for Selected Genetic Causes of Short Stature” is a Phase 2 study currently open at Children’s National Hospital. This study will target five types of genetic short stature including SHOX deficiency, hypochondroplasia, Rasopathies (which includes Noonan syndrome), heterozygous NPR2 defects and CNP deficiency.

Thirty-five children with short stature will be enrolled and followed for a six-month observation period to obtain baseline growth velocity, safety profile and quality of life assessment. Study participants will then be treated with vosoritide for 12 months and will be assessed for safety and improvement in growth outcomes.

“Many patients who present with short stature likely have genetic defects in genes involved in growth plate physiology. Those patients with selected causes of short stature that interact with the CNP pathway may benefit from treatment with vosoritide, which directly targets the growth plate,” said Andrew Dauber, M.D., MMSc., lead investigator of this clinical study and chief of Endocrinology at Children’s National Hospital, a program ranked in the top 10 by U.S. News & World Report. “In this study, our goal is to understand if vosoritide may be a safe and effective treatment option for certain genetically defined short stature syndromes.”

This clinical trial has been approved by the FDA and funded by BioMarin. Children’s National is the only site in the world offering this therapy for patients with these conditions. The study is currently underway and subject recruitment is ongoing. There are 9 participants enrolled to date.

“This study could fundamentally change the way we treat certain growth disorders”, says Dr. Dauber.

For more information on the clinical trial, click here.

Research & Innovation Campus

Boeing gives $5 million to support Research & Innovation Campus

Research & Innovation Campus

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus.

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus. The campus, now under construction, is being developed on nearly 12 acres of the former Walter Reed Army Medical Center. Children’s National will name the main auditorium in recognition of Boeing’s generosity.

“We are deeply grateful to Boeing for their support and commitment to improving the health and well-being of children in our community and around the globe,” said Kurt Newman, M.D., president and CEO of Children’s National “The Boeing Auditorium will help the Children’s National Research & Innovation campus become the destination for discussion about how to best address the next big healthcare challenges facing children and families.”

The one-of-a-kind pediatric hub will bring together public and private partners for unprecedented collaborations. It will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.

“Children’s National Hospital’s enduring mission of positively impacting the lives of our youngest community members is especially important today,” said Boeing President and CEO David Calhoun. “We’re honored to join other national and community partners to advance this work through the establishment of their Research & Innovation Campus.”

Children’s National Research & Innovation Campus partners currently include Johnson & Johnson Innovation – JLABS, Virginia Tech, the National Institutes of Health (NIH), Food & Drug Administration (FDA), U.S. Biomedical Advanced Research and Development Authority (BARDA), Cerner, Amazon Web Services, Microsoft, National Organization of Rare Diseases (NORD) and local government.

The 3,200 square-foot Boeing Auditorium will be the focal point of the state-of-the-art conference center on campus. Nationally renowned experts will convene with scientists, medical leaders and diplomats from around the world to foster collaborations that spur progress and disseminate findings.

Boeing’s $5 million commitment deepens its longstanding partnership with Children’s National. The company has donated nearly $2 million to support pediatric care and research at Children’s National through Chance for Life and the hospital’s annual Children’s Ball. During the coronavirus pandemic, Boeing fabricated and donated 2,000 face shields to help keep patients and frontline care providers at Children’s National safe.