PolicyLab Impact Report, CHI-RON Study, Allergic March, Alzheimer’s Risk

 

PolicyLab celebrates its 15th anniversary with the release of its 2023 Impact Report, and researchers receive a multimillion dollar grant to develop new therapies for rare newborn genetic diseases in our weekly news roundup. Highlights from the latest scientific publications cover patterns and prevalence of allergic diseases in children, and the development of a tool helps predict Alzheimer's risk in ethnic populations. Find out about a milestone for CHI-RON study recruitment, and learn who received a grant from the Arthritis Foundation for pediatric rheumatology research.

Celebrate PolicyLab's 15th Anniversary with its 2023 Impact Report

Alonzo South

The mission of PolicyLab, a Center of Emphasis at Children's Hospital of Philadelphia, is to achieve optimal child health and well-being by informing program and policy changes through interdisciplinary research. In conjunction with the release of the 2023 Impact Report, PolicyLab also celebrates its 15th anniversary this fall.

"PolicyLab is a trusted partner for fostering community impact," said Alonzo South, assistant vice president of Community Impact at CHOP. "Their research and guidance help my team prioritize health needs to address among youth, select community partners for collaboration, and evaluate impact of programs that support families in Philadelphia and beyond."

Research highlights from the report include the launch of the inaugural Community Partnerships in Research Program, which provides the Joint Pilot Project Award and Partnership Development Award to promote health equity in Philadelphia by encouraging and deepening community-academic partnerships. The Center also welcomed its first postdoctoral fellow: Asiya Validova, PhD. In her role, Dr. Validova participates in research on child health issues at the intersection of health insurance coverage, health services, and social determinants of health.

Check out the 2023 Impact Report to learn more about PolicyLab's programs that strive to produce a positive impact on families' health and well-being within the community.

CHOP and Penn Medicine Receive $26 Million Grant to Study Rare Genetic Diseases

A five-year $26 million grant from the National Institutes of Health (NIH) will help CHOP and Penn Medicine researchers develop new therapies using CRISPR gene editing tools for three rare, incurable genetic diseases that affect newborns in the first weeks and months after birth.

Their research will focus on phenylketonuria (PKU), hereditary tyrosinemia type 1 (HT1), and mucopolysaccharidosis type 1 (MPSI), commonly known as Hurler's syndrome. Previous studies have demonstrated that it may be possible to treat these diseases by correcting the disease-causing genetic mutations in patients' liver cells.

"CRISPR offers the potential to develop highly effective treatments for incurable genetic diseases and improve the quality of life for patients with these conditions," said co-PI William Peranteau, MD, an attending surgeon in the Center for Fetal Diagnosis and Treatment at CHOP, where he holds the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery. "This NIH funding will help us develop and validate the safety of new gene therapies that can be given to patients in vivo — directly in the body — so that we will have the data we need to be able to move into clinical trials."

PKU causes an amino acid, called phenylalanine, to build up in the body, and a late diagnosis can lead to severe intellectual disability, seizures, and psychiatric issues. HT1 is a genetic disorder that leads to disruptions in the breakdown of the amino acid tyrosine — a component in the production of brain chemicals such as dopamine, thyroid hormones, and melanin, that, if untreated, can lead to serious health problems or even death. MSPI causes an inability to produce enough enzymes to break down sugar molecules, and as the molecules build up in the body, they can cause hearing and vision loss, impaired growth, and early death.

Read more in this CHOP news release.

CHOP Researchers Validate 'Allergic March'

In the largest study of its kind, CHOP researchers provide an important overview of patterns and prevalence of allergic diseases in children. The findings, published in Pediatrics, are crucial in validating what is known as the "allergic march," in which allergies first present as eczema, followed by food allergies, asthma, and environmental allergies.

Researchers also found that a rare food allergy called eosinophilic esophagitis (EoE), which has historically been considered a disease affecting primarily white males, is more common among non-white patients than previously reported.

Senior author David Hill, MD, PhD, of the Division of Allergy and Immunology, and colleagues used the Comparative Effectiveness Research through Collaborative Electronic Reporting (CER2) Consortium database to analyze health records from more than 200,000 pediatric patients with a focus on five allergic diseases: eczema, IgE-mediated (anaphylactic) food allergy, asthma, allergic rhinitis (hay fever), and EoE. For each condition, they determined the age at diagnosis and whether and when patients presented with other allergic conditions.

"Prior studies have gauged the prevalence and patterns of allergies based on surveys completed by families," said first author Stanislaw J. Gabryszewski, MD, PhD, a fellow in the Division of Allergy and Immunology. "By using data from electronic health records, we were able to analyze data from medical providers, which allowed us to examine population-level patterns over time and in a way that minimizes reporting bias."

Researchers found that 13.4% of children had two allergic conditions, and patients with respiratory allergies, such as asthma and allergic rhinitis, tended to present with both conditions as well as other allergic conditions, suggesting symptoms could be indicative of other emerging allergies. Onset occurred at the average peak age of 4 months for eczema, 13 months for anaphylactic food allergies, 13 months for asthma, 26 months for allergic rhinitis, and 35 months for EoE.

Learn more in this CHOP press release.

Tool Developed to Help Predict Alzheimer's Risk in Various Ethnic Populations

CHOP researchers created an algorithm to help predict the risk of developing Alzheimer's disease based on genetic information in patients with a wide variety of ethnic backgrounds. By using data from globally diverse populations, this tool may be more accurate than existing methods and aims to eliminate disparities in diagnosis of the disease. The journal Alzheimer's and Dementia published the findings.

"The IHCC cohorts represent an incredibly rich resource for collaborative research with a trans-ethnic focus that will help alleviate largely neglected populations and their unique health needs," said senior author Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics. "We believe with more validation and efforts from additional diversity cohorts, this model could be applied to a range of diseases to improve healthcare services for patients who may have been underrepresented in clinical research."

Since previous studies using genomic informed risk assessment (GIRA) algorithms to identify genetic variants associated with Alzheimer's disease have been mostly carried out in white patients of European ancestry, the CHOP research team developed a GIRA algorithm to represent a wide variety of ancestries to eliminate potential discrepancies and biases in how the tool is used to help patients. This new GIRA algorithm assessed Alzheimer's risk based on variants of the apolipoprotein E (APOE) gene — implicated in Alzheimer's risk — as well as polygenic risk scores by other genomic markers and other variables including age, sex, and ethnicity.

The GIRA model performed better than polygenic risk scores alone in East Asian populations from Japan and Korea, and in South Asian populations of Pakistani and Bangladeshi origin. Although the study lacked a well-phenotyped Alzheimer's disease cohort of African origin, the current polygenic risk score system was additionally validated in people from different regions of Africa. The authors also worked with the Davos Alzheimer's Collaborative and plan to recruit more people of African ancestry to the cohort to further study their Alzheimer's risk.

Learn more in a CHOP press release.

CHI-RON Study Nears Recruitment Deadline and Meets a Major Milestone

Emily Ruckdeschel, MD

The Congenital Heart Initiative: Redefining Outcomes and Navigation to Adult-Centered Care (CHI-RON) study — supported by a $4.9 million award from the Patient-Centered Outcomes Research Institute (PCORI) — aims to fill in knowledge gaps about the care of people with congenital heart disease (CHD) as they age. The study includes 14 partner institutions and has met and surpassed the 75% recruitment milestone. Emily Ruckdeschel, MD, is the principal investigator at CHOP's study site.

The goal for CHI-RON, and the larger Congenital Heart Initiative (CHI), is to become a resource for patients and researchers, a place where they can learn more about what it means for adults who had their hearts repaired in childhood to live a long, healthy life.

CHI-RON and CHI now have enough participants to allow researchers to complete some important studies about pregnancy, mental health, and long-term healthcare follow-ups, all of which will kick off within the next year. The research teams will engage centers across the United States to better determine the needs of individual Adult Congenital Heart Association (ACHA) researchers and to understand how the CHI can help.

Participants in the CHI-RON study benefit from the larger Congenital Heart Initiative registry where participants receive regular newsletters that highlight study findings. The ACHA collaboration also has given registry participants the opportunity to interact with the patient community — a key request identified as important based on input from people who have already registered.

The study draws on the vast health data resources of the National Patient-Centered Clinical Research Institute (PCORnet®), which includes health records for 66 million patients available for observational studies.

People 18 years old or older who have a CHD diagnosis can sign up to participate via the current 14 participating research sites.

CARRA-Arthritis Foundation Grant Aims to Improve Pediatric Rheumatology Care

Sarah Bayefsky, MD

Partnering with the Childhood Arthritis and Rheumatology Research Alliance (CARRA), the Arthritis Foundation awarded 10 grants, totaling nearly $1.2 million, for investigators to address specific research gaps in juvenile arthritis and other childhood rheumatic diseases.

Sarah Bayefsky, MD, a fellow in the Division of Rheumatology, received the CARRA-Arthritis Foundation Fellow Grant for her work titled "Exploring the Care Provided by Adult Rheumatologists to Pediatric Patients: A Qualitative Study."

Dr. Bayefsky will interview families of pediatric patients who receive care from adult rheumatologists, as well as adult rheumatologists who care for children, to understand how these families and physicians approach the process of receiving and providing care, respectively, in this setting. Participants will be selected from a variety of settings and backgrounds, including diverse geographic regions within the United States. These interviews will provide physician and caregiver perspectives that will inform strategies at local, state, and national levels to improve the care children receive from adult rheumatologists.

"This study was borne out of my experience in the Internal Medicine-Pediatrics program for adult and pediatric rheumatology, in which I observed differences and similarities in the knowledge, skills, and attitudes of pediatric and adult rheumatologists regarding the care of pediatric patients," Dr. Bayefsky said. "I am very grateful for the award because it will allow me to amplify the voices of two populations that are currently minimally represented in rheumatology research. The participants' insights will be used to inform interventions aimed at ensuring high quality care by adult rheumatologists to pediatric patients."

Read more about the award in this announcement from the Arthritis Foundation.

ICYMI

Catch up on our headlines from our July 27 In the News:

• CHOP Reaches Major Milestone for CAR T Therapy
• CHOP Researcher Named 'Young Innovator' for Airway Disorder Research
• American Academy of Nursing Honors CHOP Nurse Leader as Living Legend
• Researchers Reveal Link Between NSAIDs and C. difficile Infection Severity
• Interpersonal and Structural Stigmas Increase Suicide Risk for Sexual Minority Youth

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