Foundational Gift, Gates Grant, Community-engaged Research

 

In this week's news roundup, we're highlighting the support behind breakthroughs at Children's Hospital of Philadelphia. Read about plans to use an anonymous gift to create a new center for rare neurological diseases, a Gates Foundation grant to propel mitochondrial research, PolicyLab's community-engaged research grant recipients, an investigator's findings related to underreported symptoms in children with epilepsy, and a pilot grant that helped develop preliminary findings on measles serostatus.

$25 Million Donation to Support Creation of New Research Center

An anonymous donor gifted $25 million to CHOP and Penn Medicine, in honor of the late television executive Daniel B. Burke, whose son, Stephen, served on the board of trustees at CHOP. The funds will establish the Center for Epilepsy and Neurodevelopmental Disorders (ENDD), in which scientists and clinicians will collaborate on groundbreaking research to advance genetic therapies for rare neurodevelopmental disorders.

Benjamin Prosser, PhD, associate professor of Physiology at the Perelman School of Medicine at the University of Pennsylvania, will lead the new center as director. Beverly Davidson, PhD, director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics and chief scientific strategy officer at CHOP and professor of Pathology and Lab Medicine at Penn, and Ingo Helbig, MD, a pediatric neurologist in the Department of Neurology at Penn and Division of Neurology at CHOP, and the director of Genomic Science at CHOP's Epilepsy NeuroGenetics Initiative (ENGIN) will serve as co-directors.

ENDD will focus primarily on developing therapies for disorders related to mutations of the STXBP1 and SYNGAP1 genes, which are associated with abnormal brain function, intellectual disabilities, and epilepsy. These disorders affect more than 5,000 children born each year, including Dr. Prosser's daughter, Lucy, who was diagnosed with a rare genetic neurodevelopmental disorder shortly after her birth in 2018.

"As a scientist and as a parent, I am incredibly grateful for this gift, which will propel our work forward with the hope of changing the course of these disorders," Dr. Prosser said. "We have a rare opportunity with such a brilliant and dedicated team of scientists and clinicians at Penn and CHOP, who are motivated each day to make a difference for Lucy and children like her."

ENDD strengthens an existing partnership between Drs. Prosser, Davidson, and Helbig.

"We are extremely grateful for this visionary gift that supports our efforts to solve the unsolvable when it comes to rare diseases, improving our ability to translate new discoveries about potential therapies into clinical practice," said Madeline Bell, President and CEO of Children's Hospital of Philadelphia. "CHOP and Penn have systematically invested in integrated care programs for genetic epilepsies and neurodevelopmental disorders. 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."

Read more in the CHOP news release.

CHOP Receives First Grant from Gates Foundation

With generous funding from the Bill and Melinda Gates Foundation, Douglas Wallace, PhD, geneticist and evolutionary biologist, is leading a team of researchers in the Center for Mitochondrial and Epigenomic Medicine (CMEM) to determine why certain individuals and populations have more severe symptoms to SARS-CoV-2 infection than others.

The CMEM focuses on understanding and potentially treating a broad spectrum of diseases by focusing on mitochondria, the "powerplants" of our cells. The genes for generating mitochondria are dispersed across both the nuclear DNA and the mitochondria DNA. CMEM is studying alterations in the mitochondrial genes in diseases as diverse as neuropsychiatric disorders from autism to Alzheimer's disease, blindness, heart and muscle disease, diabetes and obesity, as well as SARS-CoV-2 infection.

Since the beginning of the pandemic, the CMEM team in conjunction with the COVID-19 International Research Team, have demonstrated that SARS-CoV-2 has a striking adverse effect on mitochondrial gene expression and function. CMEM investigators will now determine if mtDNA variation contributes to individual COVID-19 sensitivity.

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

Program Supports Community-engaged Research Initiatives

PolicyLab launched the Community Partnerships in Research Program, which aims to fund community-engaged research pilot grants to promote health equity in the Greater Philadelphia area. The program has two grant mechanisms to support community-academic partnerships designed for research projects targeting health improvements for children and their families.

The Joint Pilot Project Award supports established partnerships working on research that may result in preliminary data or programs for future competitive grant applications. Rachel Myers, PhD, MS, research scientist and co-director of Community Violence and Trauma Support Programs at the Center for Violence Prevention, and Ronna Kassel, executive director of the Christian Street YMCA, are the first recipients, and will use community-based programming to help staff understand and sustain trauma-informed approaches.

The Partnership Development Award provides funding for projects related to the development of new or budding community-academic research partnerships. CHOP physicians Daniela Brissett, MD, and Nadia Dowshen, MD, MSHP, and Education Consultant and Executive Director at We.Reign Inc. Tawanna Jones Morrison, EdD, will examine the resilience of Black girls in response to institutional stereotypes.

Tara Dechert, MS, a program manager at PolicyLab, and Shukriyyah Mitchell, BSN, RN, senior director of outreach and advocacy at the National Nurse-Led Care Consortium, will build an advisory council to ensure the community of home-visited clients' voices are present in implementation, recruitment, and outreach efforts, as well as research and quality improvement.

Shelby Davies, MD, a PolicyLab faculty member and attending physician in the Division of Adolescent Medicine at CHOP, and Lynette Medley, MEd, founder and chief executive officer of No More Secrets Mind Body Spirit Inc. and co-chief executive officer and founder of the SPOT Period, will create a research partnership infrastructure to better understand the relationship between food insecurity and period poverty.

"I am proud of where we have landed and grateful for all we have learned," Meredith Matone, DrPH, MHS, scientific director at PolicyLab, wrote in a blog announcing the grant recipients. "There are many exciting avenues for growth and collaboration for these grants moving forward. I look forward to watching this program take root and seeing the number of research partnerships in our community grow."

Read more about the grants and this year's recipients in the PolicyLab blog.

Neurological Disease Concept Models Help Improve Quality of Life

Researchers in the Epilepsy NeuroGenetics Initiative (ENGIN) Frontier Program have delved into how common genetic epilepsies and neurological disorders may affect the everyday lived experience of patients and their families. Symptoms beyond neurological symptoms associated with these disorders were previously underreported and therefore poorly understood. Scientists led by Ingo Helbig, MD, and his team have created a comprehensive disease concept model that maps these symptoms and their effects to help improve quality of life and to assist in clinical care practices.

Although developmental delays and seizures are the symptoms most often linked to STXBP1 disorders, researchers also identified key underreported issues such as gastrointestinal and respiratory symptoms, and pain that affected the autonomy, socialization, and schooling of children affected by the disorders. As a result, caregivers experienced strain on their emotions and level of support, which affected daily life and activities. The goal of developing this framework is to help clinicians understand overall symptom burden for one of the most common genetic epilepsies diagnosed in children.

"In addition to describing the full range of the lived experience, our study also captured an important difference between healthcare providers and caregivers, which shows just how important it is to make sure the people who deal with these conditions every single day have their voices heard," Dr. Helbig said.

Learn more about the research in Epilepsia Open and the CHOP news release.

Mentored Research Pilot Grant Supports Findings on Maternally Derived Antibodies

A team of CHOP researchers, led by Dustin Flannery, DO, MSCE, and Karen M. Puopolo, MD, PhD, investigated how some newborns may lack maternally derived, placentally transferred measles antibodies, leaving them unprotected; the routine measle-mumps-rubella vaccine is administered at 12 months of age.

Their pilot study found that one in five newborns are missing these crucial maternally derived measles antibodies. Seeking to fill a gap in current data on measles serostatus in parturient people, the study also sought to determine if rubella serostatus could serve as a substitute for the missing measles antibodies. Their findings determined rubella antibodies were a poor surrogate, suggesting more research is needed to better protect infants who are not yet immunized.

"The team plans to perform similar seroepidemiology studies in the future for pregnant women and newborns related to Group B Streptococcus (funded by the CDC), respiratory syncytial virus, SARS-CoV-2, cytomegalovirus, and more," Dr. Flannery said.

The CHOP Research Institute Mentored Research Pilot Grant Opportunity for Junior Faculty provided funding for this research. The pilot grants aim to stimulate new research initiatives between CHOP-based assistant professors and established PIs based at CHOP or any University of Pennsylvania School and to provide additional mentoring and research opportunities to assistant professors.

Their findings appear as a Research Letter in JAMA.

ICYMI

Catch up on our headlines from our Feb. 3 In the News:

• Community-Driven Research Day Brings Organizations Together
• CRISPR 10th Anniversary Articles in USA Today Feature Beverly Davidson, PhD
• Novel Tool Allows More Accurate Long-Read RNA Sequencing
• Study Image Wins Development Cover of the Year Award

Keep up with our news, stories, and updates in real time by following us on Twitter, LinkedIn, or Instagram. Meet the minds behind the science in the Bench to Bedside podcast. Or subscribe to our newsletter to get an email sent every other Friday by signing up here.