Amplifying Our Impact and Expanding Opportunities

A $25 million gift from an anonymous donor to Children's Hospital of Philadelphia and Penn Medicine established the Center for Epilepsy and Neurodevelopmental Disorders (ENDD), accelerating collaborative research in genetic therapies for neurodevelopmental disorders. This gift will bolster the efforts of an interdisciplinary group of clinicians and scientists at CHOP and the Perelman School of Medicine at the University of Pennsylvania, led by director Benjamin Prosser, PhD and co-directors Beverly Davidson, PhD, and Ingo Helbig, MD.

ENDD will initially focus on developing therapies for disorders related to mutations of the STXBP1 and SYNGAP1 genes — which are linked to abnormal brain function, intellectual disability, epilepsy, and motor and behavioral impairments — with the goal of expanding its efforts to other genetic neurodevelopmental disorders over time.

"CHOP and Penn have systematically invested in integrated care programs for genetic epilepsies and neurodevelopmental disorders," said CHOP President and Chief Executive Officer Madeline Bell. "This new Center will fill the gap between the tremendous advances in early diagnosis and comprehensive clinical care and the development of new treatments for these patients."

After their daughter underwent multiple, life-saving surgeries at Children's Hospital of Philadelphia during the first few weeks of her life, Ed and Kristin Topolewski felt compelled to give back. Their multimillion-dollar gift will further advance both clinical and basic science research at CHOP that is finding new solutions for children with complex heart valve diseases.

The funding has established the Topolewski Pediatric Heart Valve Center as well as the inaugural Topolewski Endowed Chair in Pediatric Cardiology, which is held by Matthew Jolley, MD, an attending physician in pediatric cardiac anesthesia and echocardiography.

In addition to Dr. Jolley's research, which uses 3D image-based computer modeling to inform surgical and interventional planning in children with heart abnormalities, the funding will help to support other projects, including minimally invasive techniques, innovations in imaging, and therapeutics.

"Heart valve abnormalities are very common in children, and yet, they can be some of the most challenging disorders to treat," said Joseph Rossano, MD, MS, co-director of the Cardiac Center and chief of the Division of Cardiology at CHOP. "Having better models of these diseases and understanding the mechanisms that are leading to valve failure will have a profound impact on how we treat these patients."

Affecting one in every 3,000 people, neurofibromatosis type 1 (NF1) is one of the most common cancer predisposition syndromes that you've likely never heard of.

This year, the Gilbert Family Foundation established by Dan and Jennifer Gilbert, committed $5 million to fund three new CHOP projects focused on understanding the biology and discovery of new immunotherapy targets for brain tumors associated with NF1. The projects will be led by Chelsea Kotch, MD, MSCE, a pediatric neuro-oncologist; John Maris, MD, a pediatric oncologist and Giulio D'Angio Chair in Neuroblastoma Research; and Thomas De Raedt, PhD, a research scientist.

Dr. Kotch's projects will focus on gathering large-scale, quality data on patients with NF1 to establish standard-of-care guidelines and to inform further epidemiological studies. The project led by Dr. Maris and Dr. De Raedt will identify unique peptides in NF1 tumors that the research team can potentially target with CAR T-cell therapy.

"Not only do we have the help of the NF1 patient community, but we have the knowledge, support, and infrastructure of the wider research community at CHOP and Penn," Dr. De Raedt said, "and I think that's really what makes us unique."

Children's Hospital of Philadelphia received its first grant from the Bill & Melinda Gates Foundation this year. The multimillion-dollar funding will propel critical mitochondrial research to answer the question: Could genes of the DNA within the mitochondria, called mtDNA, lead to more severe symptoms associated with SARS-CoV-2 infection than others?

Since the beginning of the pandemic, researchers from CHOP's Center for Mitochondrial and Epigenomic Medicine (CMEM) and the COVID-19 International Research Team (COV-IRT) have demonstrated that SARS-CoV-2 has a striking adverse effect on patients' mitochondrial function.

Armed with this information, CMEM investigators will now determine if different mtDNAs affect individual sensitivity to COVID-19 by using cell lines they've developed that represent most of the major mtDNA lineages from around the world, as well as mouse models.

"With this transformative grant from the Gates Foundation, we hope to not only determine the importance of mtDNA variation in COVID-19 severity, but also to identify new approaches for mitigating the adverse impact of COVID-19," said Douglas Wallace, PhD, director of CMEM.