Honors for Investigators, Annual Meeting Highlights, Gene Editing Success

 

In this edition of In the News, innovative Children's Hospital of Philadelphia investigators receive big honors, researchers report new findings on the role of healthcare providers in autistic adolescents' transition to adulthood, and early results of a gene-editing trial for inherited blindness showcase opportunity in this new treatment approach. We also feature highlights from the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting being held May 7-11 and the Pediatric Academic Societies (PAS) Meeting held May 2-6.

American Thoracic Society Recognizes Martha Curley, RN, PhD, FAAN

Congratulations to Martha A.Q. Curley, RN, PhD, FAAN, the 2024 recipient of the Research Innovation and Translation Achievement Award from the American Thoracic Society (ATS).

Dr. Curley is the Ruth M. Colket Endowed Chair in Pediatric Nursing Science at CHOP and a professor of Nursing at Penn Nursing. The ATS is honoring her contributions to real-world innovation with tangible benefits to address unmet respiratory healthcare needs. The award also recognizes her accomplishments and role as a leader pursuing team science through interdisciplinary and inter-institutional collaborative approaches.

Dr. Curley will receive the award during the ATS 2024 Conference Tuesday, May 21, at the San Diego Convention Center.

Healthcare Providers Critical to Autistic Adolescents Preparing for Adulthood

Researchers with the Center for Injury Research and Prevention (CIRP) and the Center for Autism Research (CAR) found that healthcare providers are a crucial resource for autistic adolescents and their families as they transition to adulthood, which may include learning to drive. Their findings appear in the Journal of Autism and Developmental Disorders.

"Providers recognize their role in coaching and preparing young people and their families to navigate developmental milestones, such as licensure and driving, while also identifying the need for multidisciplinary teams and resources tailored to meet individual needs," said Rachel K. Myers, PhD, lead author of the study, associate director and a scientist at CIRP.

Investigators conducted in-depth interviews about independence, driving, and transportation with 15 healthcare providers aiding autistic adolescents and their families. The findings highlighted the importance of understanding how autistic adolescents and their families view autonomy. It also demonstrated the crucial role healthcare providers play in fostering collaborative decision-making around key milestones for adulthood, along with support strategies to help families assess driving readiness.

This study builds on the authors' prior research, which found that individualized training is a critical component for autistic adolescents in obtaining a driver's license. Licensure can promote independence and mobility and potentially lead to improved access to educational, occupational training, social, and community engagement opportunities.

The authors continue to study pathways to independence for autistic adolescents and their families. When driving is determined to not be an ideal or safe option, the research team is considering alternative ways communities can support independence and ensure participation in activities critical to adulthood. Resources for families helping autistic youths transition to adulthood are available through the PASSAGE Program and Teen Driver Source.

Learn more in this CHOP news release.

Gene Editing Successful for Two Patients with Inherited Blindness

A multi-institutional Phase 1/2 clinical trial involving researchers from CHOP and the Scheie Eye Institute at the University of Pennsylvania found that CRISPR-Cas9 gene editing delivered to 14 individuals with a form of inherited blindness was safe. The therapy also led to measurable improvements in vision in nearly half of the participants treated, including the two children treated at CHOP.  The findings appear in the New England Journal of Medicine.

"Our patients are the first congenitally blind children to be treated with gene editing, which significantly improved their daytime vision," said Tomas S. Aleman, MD, site principal investigator at CHOP and study co-author. "Our hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision."

The Phase 1/2 BRILLIANCE clinical trial included 12 adults and two children born with a form of Leber Congenital Amaurosis caused by CEP290 gene mutations, the leading cause of inherited blindness that takes place during the first year of life. The mutations cause dysfunction in the rod and cone photoreceptors in the eye's retina, which leads to irreversible vision loss.

Participants received a single injection of a CRISPR/Cas9 genome editing therapy called EDIT-101 (Editas Medicine Inc.) in one eye. As the first to deliver CRISPR-based experimental medication to the eye, this trial focused primarily on safety with a secondary analysis for efficacy. Participants were monitored every three months for at least six months at the time of the report with follow-ups ongoing.

Dr. Aleman, a pediatric ophthalmologist at CHOP and the Irene Heinz-Given and John LaPorte Research Professor in Ophthalmology at the Penn Medicine Scheie Eye Institute, said the trial represents a landmark in the treatment of genetic diseases, specifically genetic blindness. The investigative therapy offers a potential alternative treatment when traditional forms of gene therapy are not an option.

Learn more in this CHOP news release.

American Gastroenterological Association Honors Dr. Kathyrn Hamilton

The American Gastroenterological Association (AGA) honored Kathryn Hamilton, PhD, with the Young Investigator Award in Basic Science. Dr. Hamilton's research focuses on RNA-binding proteins in the intestinal response to injury and inflammation. In parallel, she is emerging as a nationally recognized investigator in the use of patient-derived organoids for the study of pediatric intestinal diseases.

Dr. Hamilton is an investigator with the Inflammatory Bowel Disease Center and the Division of Gastroenterology, Hepatology, and Nutrition at CHOP, and an assistant professor of Pediatrics. She is devoted to training and mentoring, particularly women and those from underrepresented backgrounds. The AGA award recognizes her outstanding research achievements.

Read more about the Young Investigator awardees on the AGA website.

ASGCT Annual Meeting Welcomes CHOP Innovators

CHOP Research Institute leaders in cell and gene therapy shared their expertise at the ASGCT 27th Annual Meeting in Baltimore. Beverly Davidson, PhD, chief scientific strategy officer and director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at CHOP, presented "Unlocking the Power of AAVs for Brain Gene Therapies" at the George Stamatoyannopoulos Memorial Lecture as a keynote speaker.

Dr. Davidson's research is focused on genetic diseases affecting the brain. Her lab team works with advanced molecular methods, sequencing, and imaging modalities to study the mechanisms by which mutant gene products contribute to disease, and why certain brain regions are more susceptible. Dr. Davidson's lab also is engaged in the development of next-generation therapeutics for inherited disorders, including the engineering of novel gene therapy vector capsids and cargo to approach tissue and cell type specific treatments.

Additional CHOP Speakers included Evan Weber, PhD, Division of Oncology; Johannes van der Loo, PhD, Raymond G. Perelman Center for Cellular and Molecular Therapeutics and Clinical Vector Core; Ben Samelson-Jones, MD, PhD, Division of Hematology; Susan Matesanz, MD, Division of Neurology; and William Peranteau, MD, Department of Surgery.

Katherine High, MD, a pioneer in gene therapy investigation known for her studies in adeno-associated viral-mediated gene therapy for hemophilia, received the ASGCT Founders Award. The award is among the society's highest honors and recognizes a ground-breaking contributor to the gene and cell therapy field. During her two decades at CHOP, Dr. High made a significant impact on advancing the gene therapy research program and infrastructure. Currently a visiting professor at The Rockefeller University in New York City, Dr. High presented a keynote lecture highlighting the accomplishments that led to the award.

The ASGCT's membership consists of scientists, physicians, patient advocates, and other professionals working in a wide range of academic, healthcare, nonprofit and industry settings.

Through education and awareness initiatives, ASGCT members strive to incorporate the use of genetic and cellular therapies to transform the practice of medicine and alleviate human disease.

CHOP Researchers at PAS 2024 in Toronto

Numerous CHOP investigators shared research findings in Toronto at the annual PAS Meeting, which brings together an international community of researchers, academics, clinical care providers, and community practitioners.

Morgan A. Zalot, MPH, clinical research study lead at CHOP, presented findings suggesting that the benefits of administering the rotavirus vaccine in the neonatal intensive care unit outweigh the risks. Meanwhile, Danielle Cullen, MD, MPH, MSHP, a CHOP attending physician in the Division of Emergency Medicine, shared findings that healthcare providers can more effectively connect parents and other caregivers of children to needed social resources when they present a menu of options.

Zalot conducted a yearlong prospective study in collaboration with the Centers for Disease Control and Prevention titled, "Investigation of Potential Vaccine-strain Rotavirus Transmission in a 100-bed NICU that Routinely Vaccinates: 1-year Surveillance Results." The researchers analyzed 3,448 weekly stool samples from 774 patients between January 2021 and January 2022. They found that 99.3% of non-vaccinated patients exposed to vaccinated patients did not test positive for the disease. Non-vaccinated patients that contracted rotavirus had no symptoms after 14 days.

Vaccination is important to prevent the highly contagious but preventable rotavirus, but transmission concerns often prevent vaccination in the NICU. These findings are important because some infants are too old to receive the vaccine once discharged from the NICU.

Learn more in this press release.

Dr. Cullen presented, "Socially Equitable Care by Understanding Resource Engagement (SECURE): A Pragmatic RCT," which described an alternative approach to risk-based screening commonly used to identify families facing food and housing insecurity, financial strain, and unsafe environments. A downside of risk-based screening is that it can lead to inequalities in resource distribution and usage by requiring families to disclose hardships to receive assistance.

"Children and families with social need should receive resources that reflect their priorities, not based on whether they meet the threshold of a screening tool," Dr. Cullen said.

Her research findings suggest that offering a resource menu allows for a more family-centered approach, equipping children and families with tailored social resources based on their priorities, while reducing inequalities and fear of unintended consequences that screening practices may perpetuate.

The study team provided 4,000 caregivers with either a traditional social risk screening tool, a resource menu, or no assessment. The study found that participants using the resource menu were 9.4% more likely to request resources than those using the screening tool. The beneficial effect of the resource menu was even more pronounced among families who prefer a non-English language, with more than 40% of the participants using an online resource map to access resources.

Read more in this press release.

Visit the PAS 2024 website for comprehensive list of presenters.

Researchers Identify Causal Genetic Variant Linked to Common Childhood Obesity

CHOP researchers identified a causal genetic variant strongly associated with childhood obesity. The study, published in Cell Genomics, provides new insight into the importance of the hypothalamus of the brain and its role in common childhood obesity. The target gene may serve as a druggable target for future therapeutic interventions.

"With more research, there's potential to learn how the target of this variant's action may be a target for new therapies specifically designed to treat childhood obesity," said first author Sheridan H. Littleton, PhD, a postdoctoral research associate in the Center for Spatial and Functional Genomics.

CHOP investigators led previous international genome-wide association studies that found specific genetic markers, or loci, linked with obesity. Many of these studies revealed loci associated with childhood and adult obesity in equal measure, and most of these loci have been in non-coding regions of the genome, meaning they do not code for specific proteins. This makes their mechanisms more difficult to study. This latest research focused on chr12q13, a locus harboring the FAIM2 gene that generated a stronger signal with childhood obesity when compared to adult obesity.

"This work further underscores how the brain is central to the genetics of obesity and provides us with a strategy for further study," said Struan F.A. Grant, PhD, director, Center for Spatial and Functional Genomics and the Daniel B. Burke Endowed Chair for Diabetes Research at CHOP.

Read more in the CHOP news release.

ICYMI

Catch up on our headlines from our April 26 In The News:

• Biomedical Technician Training, Asthma Diagnoses, Machine Learning
• New Gene Therapy Improves Treatment for Sickle Cell Disease
• COVID-19 Infection Not Linked to Potential Asthma Diagnoses in Pediatric Patients
• Researchers Discover Underlying Biology Behind Fontan-Associated Liver Disease
• Nature Explores Breakthrough T Cell Biology Research From CHOP Scientists
• Researchers Investigate How Machine Learning Can Impact DNA Sequencing

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