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Andrea L. Gropman

Andrea L. Gropman, M.D., FAAP, FACMG, FANA, named as the Margaret O’Malley Professor of Genetic Medicine

Andrea L. GropmanChildren’s National Hospital named Andrea L. Gropman, M.D., FAAP, FACMG, FANA, as the Margaret O’Malley Professor of Genetic Medicine at Children’s National Hospital.

Dr. Gropman serves as Chief of the Division of Neurogenetics and Developmental Pediatrics at Children’s National Hospital. She is also a Professor of Pediatrics and Professor of Neurology at George Washington School of Medicine and Health Sciences.

About the award

Dr. Gropman joins a distinguished group of Children’s National physicians and scientists who hold an endowed chair. The Margaret O’Malley Professor of Genetic Medicine is one of 47 endowed chairs at Children’s National.

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

Dr. Gropman’s research focuses on neuroimaging, inborn errors of metabolism such as urea cycle disorders and mitochondrial disorders, and neurogenetics. She is the principal investigator of the Urea Cycle Disorders Consortium (UCDC) and the UCDC imaging consortium. She is the deputy clinical director of the Mito EpiGen Program.

Thomas and Mary Alice O’Malley, through their vision and generosity, are ensuring that Dr. Gropman and future holders of this professorship will launch bold, new initiatives to rapidly advance the field of pediatric genetic medicine, elevate our leadership and improve the lifetimes of children with genetic diseases.

About the donors

Tom and Mary Alice O’Malley have partnered with Children’s National to improve the lives of patients with urea cycles disorders for more than two decades. In 2003, their transformational philanthropy helped launch the Urea Cycle Disorders Consortium. This pioneering network grew to include 16-sites worldwide. It garnered 20 years of funding from the NIH’s Rare Diseases Clinical Research Network — the only center to sustain continuous funding over this period. This consortium’s research has yielded multiple effective treatment strategies, including government approval of three lifesaving therapies.

“The O’Malley family’s steadfast generosity helped us grow into the robust community of investigators and families we are today,” says Dr. Gropman. “They transformed care for UCD patients everywhere.”

mitochondria

Grant funds study of two maternally inherited mitochondrial diseases

mitochondria

The National Institutes of Health awarded George Washington University and Children’s National Hospital a grant to study two maternally inherited mitochondrial diseases.

The National Institutes of Health awarded George Washington University and Children’s National Hospital a grant to study two maternally inherited mitochondrial diseases. Andrea Gropman, M.D., division chief of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National, along with her co-investigator, Anne Chiaramello, M.D., from the George Washington University School of Medicine, will lead the study.

The proposed studies focus on two ultra-rare maternally inherited mitochondrial diseases:

  • Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS); and
  • Leber’s Hereditary Optic Neuropathy-Plus (LHON-Plus).

Both diseases are among those studied by the Rare Diseases Clinical Research Network.

“We are really pleased to be able to change the landscape for MELAS and LHON, two mitochondrial disorders with relentless progression and no treatment,” Dr. Gropman said. “This grant represents the fruition of an eight-year collaboration with my colleague Dr. Chiaramello and we are fortunate to be able to deliver this at Children’s National and serve our patients and community.”

Because patients currently do not have access to effective therapeutic intervention, this results in significant disability, morbidity and premature death. The UG3 phase of the study will focus on translational MELAS and LHON-Plus studies and submission of an IND protocol to the Food and Drug Administration. The UH3 phase will focus on a basket clinical trial with MELAS and LHON-Plus to:

  • Provide proof-of-concept that the basket design can be applied to divergent ultra-rare diseases.
  • Advance the dataset for safety and pharmacokinetics/pharmacodynamics of our lead compound for a larger number of patients than in a conventional clinical trial setting.
  • Gather outcomes and practical information for optimizing the design of future basket clinical trial.

“Dr. Gropman is dedicated to giving children with MELAS the very best care,” said Elizabeth Wells, M.D., vice president of Neuroscience and Behavioral Medicine Center at Children’s National. “This new research funding is exciting and means more patients can benefit from the expertise she has developed at Children’s National.”

DNA moleucle

Multidisciplinary team seeks to reverse epigenetic changes associated with fetal alcohol syndrome disorder

DNA moleucle

The team hopes to optimize and develop treatments that can reverse epigenetic changes in clinical trials, paving the way to make significant progress in the field — something that is lacking to date.

A clinical team joined forces with a research team at Children’s National Hospital to help advance treatments that can improve a child’s development caused by fetal alcohol syndrome disorder (FASDs), which is a group of conditions that can occur in a person who was exposed to alcohol before birth. This boost in collaboration between the bench and clinical hopes to optimize and develop treatments that can reverse epigenetic changes in clinical trials, paving the way to make significant progress in the field — something that is lacking to date.

So far, Children’s National experts have published various pre-clinical studies that identified epigenetic changes caused by alcohol exposure during pregnancy. These changes observed in the pre-clinical models created neuropsychiatric problems like patients with fetal alcohol syndrome disorder. Now, they want to bring such potential treatments effective in pre-clinical models to the bedside.

“As a first step, we are going to test whether the epigenetic changes that were observed in pre-clinical models of FASD are also true in human patients,” said Kazue Hashimoto-Torii, Ph.D., principal investigator of the Center for Neuroscience Research at Children’s National. “We hope a small amount of blood donated by patients with FASD reveal the changes. Meanwhile, my group has also been optimizing drug candidates that reverse the epigenetic changes toward clinical trials.”

Advances in genetics and genomics have led to discoveries about the timing of exposure and developmental outcomes and genetic and epigenetic signatures that may be protective or harmful in terms of how in utero alcohol exposure affects developmental outcomes.

The hold-up in the field

While the exact number of people with FASDs is unknown, the National Institutes of Health estimates that 1% to 5% of the population have FASDs. FASDs has a spectrum of diagnoses that represent a broad range of effects that can be manifested in an individual whose mother drank alcohol during pregnancy. These conditions can affect everyone in different ways and range from mild to severe. Individuals with mild conditions may go undiagnosed. The more affected individuals have comorbid attention-deficit/hyperactivity disorder (ADHD) and behavioral problems that become the focus of clinical encounters. The individual’s health care provider may not recognize the core features as part of FASD.

“Because there is a stigma associated with drinking while pregnant, many providers fail to get this history, and women may be reluctant to offer this information,” said Andrea Gropman, M.D., division chief of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National. “There are subtle and more obvious facial dysmorphology that may help with suspicion or identification, but many individuals do not have these findings.”

The core features may be nonspecific, such as intellectual disabilities and problems with behavior and learning, difficulties with math, memory, attention, judgment and poor impulse control, which are frequent findings in ADHD, autism, learning disorders and other conditions.

“Unless history is taken and FASD is in the differential diagnosis, the diagnosis may not be made,” said Dr. Gropman. “Individuals with FASD may feel stigmatized and opt not to participate in clinical trials.”

As mentioned by Dr. Gropman, stigma can make a patient family be reluctant to seek treatment, and thus the development of treatment for FASD cannot make significant progress to date, Hashimoto-Torii added.

Children’s National Hospital leads the way in an IRB approved study

Researchers at Children’s National have identified a potential drug candidate that reverse the epigenetic changes and may lead to clinical trials. The team is seeking people to participate in an IRB approved study. The study will involve cognitive testing, filling out surveys about current functioning and cheek swab and blood sample to determine if these changes are seen in patients. To participate, subjects must be

  • Children between the ages 5-12 with prenatal alcohol exposure.
  • Mother of child recruited above.

For participation, please contact Grace Johnson, research coordinator at to screen for eligibility at 202-476-6034 or gjohnson3@childrensnational.org

Meet the multidisciplinary team with different yet complementary skills in different fields, such as basic science, medical, social sciences, neurology and developmental disabilities, and development, who are working tirelessly to address the complex health problem.

Gropman lab:

Andrea Gropman, M.D., received her medical doctorate degree from the University of Massachusetts Medical School and specializes in neurogenetics, with a focus on mitochondrial disorders and Smith Magenis syndrome. Her latest research focuses on atypical patterns of inheritance, childhood mitochondrial disorders and other inborn errors of metabolism presenting with white matter disease.

Meira Meltzer, M.A., M.S., C.G.C., genetic counselor with a demonstrated history of working in the hospital and healthcare industry. Also skilled in molecular biology, clinical research and medical education. Strong healthcare services professional with a M.S. focused on genetic counseling from Brandeis University.

Cathy Scheiner, M.D., developmental behavioral pediatrician with a special interest in attention-deficit / hyperactivity disorder (ADHD), cerebral palsy and premature infant.

Grace Johnson, research assistant.

Hashimoto-Torii Lab:

Kazue Hashimoto-Torii, Ph.D., received her postdoctoral training in the Pasko Rakic laboratory at Yale University. Her research focuses on neurobehavior problems of children that stem from their environment during development, such as prenatal exposure to alcohol, drug and high-level glucose. A few drug candidates that her lab discovered have been patented and her lab is currently working hard to bring those medicines to bedside.

Satoshi Yamashita, M.D., Ph.D., postdoctoral research fellow skilled in developmental neurobiology. He is a pediatrician with Japanese medical license and received his Ph.D. with iPS cell research for STXBP1 encephalopathy in Japan.

Chiho Yamashita, B.N., research assistant passionate about child disease research. She is a nurse with a Japanese nursing license and worked in the pediatric department in Japan.

3d render of brain form

LEND program to support physicians with interdisciplinary training for NDD and ASD

3d render of brain form

In a time with dearth of specialties, LEND will train allied health professionals, parent advocates and self-advocates, provide continuing education and technical assistance, research and consultation while preparing professionals for leadership roles in the provision of health and related care.

A new program at Children’s National Hospital, known as The Leadership Education in Neurodevelopmental and Other Related Disabilities (LEND CN), will provide interdisciplinary training to enhance clinical expertise and leadership skills while reducing the shortage of medical specialists — a hurdle also present nationwide. Participating institutions such as Children’s National Hospital, Howard University and University of the District of Columbia will enhance the care for children and families with neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD).

The program seeks to improve the health of infants, children and adolescents with or at risk for NDD and related disabilities. LEND CN will also prepare future leaders in this space that offer a comprehensive support tailored to a child’s specific condition.

“There are very few opportunities for training a broad multidisciplinary team to work with and provide leadership in the neurodevelopmental and autism space,” said Andrea Gropman, M.D., neurodevelopmental pediatrics and neurogenetics division chief at Children’s National Hospital and principal investigator of the LEND CN program. “This grant funding will allow the LEND CN leadership and curriculum team to develop innovative training and leverage community resources, universities and institutions to provide a broad, diverse and inclusive training.”

The Health Resources and Services Administration (HRSA) awarded the program with $2,200,000. The funding will help develop, implement, evaluate and innovate the curriculum and experiential activities of LEND CN. These efforts will be led by Dr. Gropman and Anne Pradella Inge, Ph.D., clinical director of the Center for Autism Spectrum Disorders at Children’s National Hospital and LEND educational content director.

In a time with dearth of specialties, LEND will train allied health professionals, parent advocates and self-advocates, provide continuing education and technical assistance, research and consultation while preparing professionals for leadership roles in the provision of health and related care.

“We have a broad multidisciplinary team of specialists in developmental pediatrics, neuropsychology, speech and hearing, and other allied health specialists,” Dr. Gropman said, adding that Children’s National is uniquely positioned to participate in this grant opportunity. “This grant is exciting because it allows us to take advantage of the full potential the D.C. area has to offer to establish comprehensive and individualized training.”

Many of the trainees of this program remain local and in the field of developmental disabilities and autism, while many others also have risen to leadership positions. Some who have completed the program return as LEND educators to the next generation of trainees, proving the many doors this program can open for those seeking a career in neurodevelopmental pediatrics and work that intersects with developmental disabilities and their families.

Andrea Gropman

$5M in federal funding to help patients with urea cycle disorders

Andrea Gropman

Andrea L. Gropman, M.D.: We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.

An international research consortium co-led by Andrea L. Gropman, M.D., at Children’s National Hospital has received $5 million in federal funding as part of an overall effort to better understand rare diseases and accelerate potential treatments to patients.

Urea cycle disorder, one such rare disease, is a hiccup in a series of biochemical reactions that transform nitrogen into a non-toxic compound, urea. The six enzymes and two carrier/transport molecules that accomplish this essential task reside primarily in the liver and, to a lesser degree, in other organs.

The majority of patients have the recessive form of the disorder, meaning it has skipped a generation. These kids inherit one copy of an abnormal gene from each parent, while the parents themselves were not affected, says Dr. Gropman, chief of the Division of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National. Another more common version of the disease is carried on the X chromosome and affects boys more seriously that girls, given that boys have only one X chromosome.

Regardless of the type of urea cycle disorder, when the urea cycle breaks down, nitrogen converts into toxic ammonia that builds up in the body (hyperammonemia), particularly in the brain. As a result, the person may feel lethargic; if the ammonia in the bloodstream reaches the brain in high concentrations, the person can experience seizures, behavior changes and lapse into a coma.

Improvements in clinical care and the advent of effective medicines have transformed this once deadly disease into a more manageable chronic ailment.

“It’s gratifying that patients diagnosed with urea cycle disorder now are surviving, growing up, becoming young adults and starting families themselves. Twenty to 30 years ago, this never would have seemed conceivable,” Dr. Gropman says. “We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.”

In early October 2019, the National Institutes of Health (NIH) awarded the Urea Cycle Disorders Consortium for which Dr. Gropman is co-principal investigator a five-year grant. This is the fourth time that the international Consortium of physicians, scientists, neuropsychologists, nurses, genetic counselors and researchers has received NIH funding to study this group of conditions.

Dr. Gropman says the current urea cycle research program builds on a sturdy foundation built by previous principal investigators Mendel Tuchman, M.D., and Mark Batshaw, M.D., also funded by the NIH. While previous rounds of NIH funding powered research about patients’ long-term survival prospects and cognitive dysfunction, this next phase of research will explore patients’ long-term health.

Among the topics they will study:

Long-term organ damage. Magnetic resonance elastrography (MRE) is a state-of-the-art imaging technique that combines the sharp images from MRI with a visual map that shows body tissue stiffness. The research team will use MRE to look for early changes in the liver – before patients show any symptoms – that could be associated with long-term health impacts. Their aim is spot the earliest signs of potential liver dysfunction in order to intervene before the patient develops liver fibrosis.

Academic achievement. The research team will examine gaps in academic achievement for patients who appear to be underperforming to determine what is triggering the discrepancy between their potential and actual scholastics. If they uncover issues such as learning difficulties or mental health concerns like anxiety, there are opportunities to intervene to boost academic achievement.

“And if we find many of the patients meet the criteria for depression or anxiety disorders, there are potential opportunities to intervene.  It’s tricky: We need to balance their existing medications with any new ones to ensure that we don’t increase their hyperammonemia risk,” Dr. Gropman explains.

Neurologic complications. The researchers will tap continuous, bedside electroencephalogram, which measures the brain’s electrical activity, to detect silent seizures and otherwise undetectable changes in the brain in an effort to stave off epilepsy, a brain disorder that causes seizures.

“This is really the first time we will examine babies’ brains,” she adds. “Our previous imaging studies looked at kids and adults who were 6 years and older. Now, we’re lowering that age range down to infants. By tracking such images over time, the field has described the trajectory of what normal brain development should look like. We can use that as a background and comparison point.”

In the future, newborns may be screened for urea cycle disorder shortly after birth. Because it is not possible to diagnose it in the womb in cases where there is no family history, the team aims to better counsel families contemplating pregnancy about their possible risks.

Research described in this post was underwritten by the NIH through its Rare Diseases Clinical Research Network.