In the News: Metabolic Disease, Concussion in Young Children

This week In The News, Children’s Hospital of Philadelphia research lays groundwork for a novel treatment for eosinophilic esophagitis, experts suggest an improved classification of vascular changes in retinopathy of prematurity, and a study team from CHOP and Penn discover a molecule’s role in insulin regulation. Investigators at CHOP also provide insights to improve outcomes for young concussion patients, the Children’s Brain Tumor Network receives a funding boost for cloud-based research, and injury science interns prepare for firsthand project experience.

Key Clinical Trial Results Support New Treatment Option for Eosinophilic Esophagitis

CHOP researchers participated in an international team who published the results of a key clinical trial that helped to inform U.S. Food and Drug Administration approval of the monoclonal antibody dupilumab for the treatment of eosinophilic esophagitis (EoE) in pediatric patients between 1 and 11 years old. Their findings appeared in the New England Journal of Medicine and built upon previous work that examined the safety and efficacy of dupilumab for adolescents and young adults with EoE.

“This manuscript and the related FDA approval finally provides a treatment option for our patients,” said study co-author Jonathan Spergel, MD, PhD, co-leader of the Food Allergy Center and section chief of the Allergy Program at CHOP and professor of Pediatrics at the University of Pennsylvania. “We are excited for our patients and new potential benefits for them.”

EoE is a chronic allergic inflammatory disease of the esophagus that causes symptoms such as redness, swelling, and itchiness. Traditional treatments such as food elimination diets, topical glucocorticoids, proton-pump inhibitors, and esophageal dilation do not provide relief for about a third of patients with EoE, and some experience negative side effects.

After growing evidence suggested type 2 cytokines play a key role in EoE, researchers began investigating dupilumab, which blocks interleukin-4 and interleukin-1, two key drivers of inflammation in patients with EoE.

In this study, no inflammation was present in 68% of patients who received higher-exposure dupilumab and 58% of patients receiving lower-exposure dupilumab. Higher-exposure dupilumab significantly improved several clinical outcomes. Sanofi and Regeneron Pharmaceuticals Inc. supported the study.

Read more in this CHOP news release. 

Ophthalmology Research Contributes to Image-based ROP Grading Scale

Gil Binenbaum, MD, MSCE

 

A group of U.S. and international experts, along with the International Classification of Retinopathy of Prematurity Third Edition (ICROP3) Committee, proposed a new classification tool for retinopathy of prematurity (ROP) called Plus (P)-Score. It is based on a nine-photo reference-image set for grading vascular changes.

“This new detailed classification will create more efficiency in the diagnosis process and give clinicians more confidence when diagnosing,” said first author Gil Binenbaum, MD, MSCE, chief of the Division of Ophthalmology and the Mabel E. Leslie Endowed Chair in Pediatric Ophthalmology at CHOP. Jocelyn He, a biostatistician at Penn, is a co-author with Dr. Binenbaum, who is also an associate professor of Ophthalmology at Penn.

While the P-Score classification tool is not meant to replace plus diagnosis for treatment decisions, the authors noted that its use in their own institutions has demonstrated better comparison between examinations for progression and regression, communication between examiners, and documentation of vascular change without fundus imaging. Additionally, they suggest that P-Score could provide more detailed ROP classification for clinical trials.

The study team published their findings in Ophthalmology.

Investigators Discover Molecule’s Mechanistic Role in Insulin Regulation

Researchers from CHOP and Penn revealed the mechanisms behind a particular molecule’s involvement in regulating insulin sensitivity. Nature Communications published the findings, which may serve as the basis for a potential therapeutic target for obesity-related type 2 diabetes.

This new study focuses on adipose tissue macrophages (ATMs), which keep the adipose tissue, commonly called body fat, healthy and functioning normally. While it was already known that ATMs secrete small vesicles with important signaling molecules meant to help prevent obesity-related metabolic disease, the underlying mechanisms were not understood.

The discovery of a micro-RNA called miR-6236 was a pivotal development in this work, as it helps to balance some harmful effects of obesity and type 2 diabetes at a cellular level. Through two preclinical models and a large data set of individuals at risk for metabolic disease, investigators confirmed that ATMs secrete miR-6236. This improves insulin sensitivity by suppressing PTEN, a gene that prior studies have linked to obesity and type 2 diabetes.

“Findings like this show that the immune system is central to a healthy metabolism, and hold promise for developing new treatments,” said David Hill, MD, PhD, an attending physician in the Division of Allergy and Immunology at CHOP and assistant professor of Pediatrics at Penn. “With this information, we could be looking into the development of synthetic micro RNAs, and in the case of miR-6236, there’s a possibility it could be given to patients to improve insulin sensitivity and reduce hyperglycemia.”

The National Institutes of Health, JPB Foundation, and CHOP Research Institute supported this work.

Learn more in this CHOP news release.

Improving Concussion Intervention and Treatment for Young Patients

Researchers in the Minds Matter Concussion Program at CHOP conducted research that showed children between the ages of 5 and 12 were more likely to experience a concussion from recreation and other non-sport activities. However, those injuries were not seen by specialists until days later compared with sports-related concussions in the same age group.

“Patients injured outside of sports and recreation experienced a higher burden of symptoms and more changes to daily life, and delays in appropriate care could exacerbate these negative effects,” said senior study author Kristy Arbogast, PhD, director of the Center for Injury Research and Prevention and co-director of the Minds Matter Concussion Program at CHOP.

In a related CIRP blog post, Dr. Arbogast explained that knowing how patients in this age group sustained their concussion can guide interventions that lead to better health outcomes. This analysis highlights the need for additional research in this area and for concussion resources outside of specialty care, such as in primary care, emergency, and school health settings, as those providers and caregivers may be the first to see a pediatric patient when they present with an injury.

Learn more in this CHOP news release.

Researchers Develop Innovative Approach for Alpha Thalassemia

Researchers at CHOP and the University of Pennsylvania developed a new model to advance therapeutic approaches for alpha thalassemia (AT) to improve patient outcomes and reduce the need for ongoing treatments. 

The study, published in Blood by researchers in the Division of Hematology including senior author Stefano Rivella, PhD, examined the possibility of using a new gene therapy to correct the lack of alpha globin that reduces the production of hemoglobin in the blood disorder.

“This innovative approach represents a much-needed step forward in the treatment of alpha thalassemia,” Dr. Rivella said. “We look forward to further research and the promise of improved patient outcomes with fewer complications over time.” 

This new treatment model utilizes an innovative lentiviral vector to express human alpha globin — ALS20al — to repair the defective genetic traits via hematopoietic stem cell modification and transplantation. The researchers found it produced high levels of ALS20al in animal models and boosted normal hemoglobin production. This vector requires further testing, but the findings of this study indicate that it could reduce the need for ongoing transfusions and reduce the symptoms of AT over time. 

In advanced cases of AT, patients will experience anemia and severe symptoms originating from a lack of oxygen to red blood cells in the body, which is especially problematic with newborns. The current treatment method requires blood transfusions on a regular basis, along with close attention and intensive care. 

Read more in this CHOP news release.

CHOP Awarded AWS Grant to Accelerate Brain Tumor Research

Amazon Web Services (AWS) awarded a $1 million grant to the Children's Brain Tumor Network (CBTN) at Children’s Hospital of Philadelphia as part of the inaugural AWS IMAGINE Grant: Children’s Health Innovation Award to harness the power of the AWS cloud to advance pediatric and children’s causes worldwide.

Adam Resnick, PhD, director of the Center for Data-Driven Discovery in Biomedicine (D3b) at CHOP that functions as the CBTN’s operations center, delivered a keynote address at the summit. Dr. Resnick highlighted the connection between artificial intelligence (AI) and brain tumor research, showcasing how innovative approaches at D3b are making a difference. This grant will significantly boost research efforts and accelerate the development of AI-driven technologies aimed at understanding and treating brain tumors.

AWS provides a place where researchers can securely manage de-identified and anonymized data while safeguarding the privacy of patients and clinical study participants. Through the co-development of a suite of cloud-based data platforms that allow researchers worldwide to access rich collections of brain tumor data, CBTN has helped accelerate the research process by enabling members of the scientific and patient communities to partner. This grant reinforces CBTN’s commitment to pioneering advancements in brain tumor research.

AWS announced the funding support during the AWS Summit in Washington, DC, held June 26-27. Learn more in this AWS news release.

Research Experiences Program Mentors Future Injury Science Professionals

The Center for Injury Research and Prevention (CIRP) at CHOP Research Institute hosts the Injury Science Research Experiences for Undergraduates (REU) program, a 10-week paid summer research internship opportunity sponsored by the National Science Foundation.

The REU program provides underrepresented students the mentorship of principal investigators and peer mentors, along with hands-on research experience to build the scientific foundation for injury interventions, translate interventions into practical solutions, and evaluate their success.

This year’s selected REU class will work on a variety of research projects in engineering, behavioral science, and epidemiology. Meet the 2024 REU participants on the Research in Action blog.

ICYMI

Catch up on our headlines from our June 21 In The News:

• CHOP Partnership Inspires Global Innovation in Pediatric Health
• Researchers Develop New Tool for Better Classification of Inherited Disease-Causing Variants
• New Deep Learning Tool Helps Identify Patterns in Spatial Transcriptomic Data
• NJ-SHO Provides Robust Resource in Population Health and Safety Data
• Gregory Tasian, MD, MSCE, Presents Data Supporting Shock Wave Lithotripsy for Kidney Stones

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