Excellence Award, Orphan Drug Designation, Imaging Technique, Coordinated Asthma Care

 

We're celebrating an excellence award that honors Yael Mossé, MD, for her transformational work in Pediatric Oncology. In other exciting research news, the U.S. Food and Drug Administration's incentive programs for rare disease drug and biologic development may help CHOP researchers streamline gene therapy for multiple sulfatase deficiency. Researchers assess a new approach to evaluating kneecap instability, and a study highlights the importance of community health workers in coordinating asthma care across different settings.

Yael Mossé, MD, Receives a 2024 Penn Medicine Award of Excellence

Yael Mossé, MD, received the William Osler Patient Oriented Research Award, one of the 2024 Penn Medicine Awards of Excellence. The award recognizes achievement for research in which an investigator directly interacts with patients who are clinical trial participants.

Dr. Mossé's groundbreaking work in anaplastic lymphoma kinase (ALK) onocogene mutations has led to enhanced treatment and outcomes for children with neuroblastoma and other solid tumors, effectively transforming the Pediatric Oncology landscape.

She leads the Neuroblastoma Developmental Therapeutics Program at CHOP, where she fosters multidisciplinary collaboration to translate genomic discoveries into clinical practice. Dr. Mossé also is a professor of Pediatrics at the University of Pennsylvania and the inaugural Patricia Brophy Endowed Chair in Neuroblastoma Research at CHOP.

Read more about the award in this CHOP news release. Visit Dr. Mossé's laboratory page to learn more about her ALK research.

FDA Designations Aim to Streamline Gene Therapy Development for Extremely Rare Diseases

The U.S. Food and Drug Administration granted both Rare Pediatric Disease designations and Orphan Drug Designations for investigational gene therapies for five rare diseases that are part of the Bespoke Gene Therapy Consortium (BGTC) sponsored by the National Center for Advancing Translational Sciences (NCATS). CHOP is a BGTC study site for multiple sulfatase deficiency, a disorder that affects the brain, lungs, skin, and skeleton with no currently approved treatments.

Commercial interest is scarce for developing gene therapies for extremely rare diseases. The FDA designations can make the opportunity to bring these therapies to market more appealing to prospective partners through financial incentives.

"These designations are important to help push rare disease research forward so our patients aren't left behind," said Rebecca Ahrens-Nicklas, MD, PhD, a physician scientist in the Division of Human Genetics who co-leads the BGTC study site at CHOP with Laura Adang, MD, PhD, MSTR, attending physician in the Division of Neurology.

The BGTC clinical trials, which are in preclinical development, will test safety and preliminary efficacy of gene therapies for eight rare diseases in small numbers of study participants. If successful, such early phase trials will set the stage for clinical studies.

The BGTC is a public-private partnership among the National Institutes of Health, the FDA, pharmaceutical and life science companies, and patient advocacy groups. NCATS is among 10 participating NIH Institutes and Centers. It helps coordinate and lead the BGTC. The Foundation for the NIH manages the BGTC as part of its Accelerating Medicines Partnership® (AMP) program.

Learn more about research conducted by Dr. Ahrens-Nicklas and Dr. Adang with the BGTC in this Cornerstone story.

Study Results Show Ultrasound Represents Reliable Imaging of Pediatric Kneecap Instability

CHOP researchers reported study results that suggest a novel measure of kneecap instability using musculoskeletal ultrasound is a reliable imaging method. They noted that the ease of access and efficiency of utilizing ultrasound within a clinic, which allows for serial measurements over time to track knee injuries and response to treatment, may be more feasible than magnetic resonance imaging.

The researchers found that based on 50 study participants — 24 with kneecap instability and 26 healthy controls — their technique using musculoskeletal ultrasound for assessing kneecap instability was consistent and reliable. More research is needed to evaluate the reproducibility of this measure.

Pediatric and adolescent athletes 10 to 17 years of age experience patellofemoral (kneecap) instability six times more often than adults, which can lead to recurrent instability and repeated dislocation.

Elliot Greenberg, PT, DPT, PhD, OCS, CSCS, a sports medicine physical therapist and researcher at CHOP, is first author of the study. J. Todd Lawrence, MD, PhD, pediatric orthopedic surgeon; Naomi Brown, MD, FAAP, CAQSM, pediatric sports medicine specialist; and Brendan A. Williams, MD, pediatric orthopedic surgeon, were also part of the research team.

Their findings appear in the Orthopaedic Journal of Sports Medicine. Learn more in this CHOP news release.

Community Health Workers Critical to Coordinated Asthma Care Across Lived Environments

CHOP investigators conducted a hybrid effectiveness and implementation trial to determine if the involvement of community health workers (CHW) in care coordination across school, home, and primary care settings could improve asthma control for minority, low-income children.

"We have to think about a holistic and connected approach to reducing asthma across all environments a child may encounter," said first author Tyra Bryant-Stephens, MD, Medical Director of the Community Asthma Prevention Program and Chief Health Equity Officer of the Center for Health Equity at CHOP. "We want to make sure there is evidence-based asthma care wherever children may be and that everyone is taking steps to make every environment a healthier one."

The study team analyzed outcomes of the combined interventions, including asthma management, trigger remediation, and care coordination, that CHWs conducted in primary care offices, homes, and 36 public and charter schools in West Philadelphia. Study participants included 626 children between the ages of 5 to 13 years old with uncontrolled asthma from May 2018 to June 2022, 96% of whom self-identified as Black and 98% as non-Hispanic.

All groups had statistically significant improvements in asthma control from baseline to 12 months, which provides preliminary evidence supporting the impact of CHWs' linkage of evidence-based asthma care across different environments.

JAMA Pediatrics published the findings. Learn more in this CHOP news release.

Preclinical Study Shows Emicizumab Could Improve Clotting for Hemophilia B Patients With Specific Variants

CHOP researchers studied how emicizumab, a widely used drug to treat hemophilia A, could affect blood clotting ability for patients with hemophilia B-related factor IX (FIX) variants in a preclinical study. The team screened 105 hemophilia B-causing FIX variants and found 41 demonstrated improved clotting with emicizumab. They confirmed the results by similarly demonstrating improved clotting in patient samples.

"Our research offers hope that these new treatments could eventually improve the quality of life for pediatric patients with select hemophilia B gene types, especially young children where intravenous administration is very challenging," said Benjamin Samelson-Jones, MD, PhD, a core member of the Novel Therapeutics for Bleeding Disorders (NoT Bleeding) Frontier Program team and an attending physician in the Division of Hematology .

Hemophilia is a genetic disorder in which blood doesn't properly clot due to missing or low levels of "clotting factors," which can lead to excessive bleeding. Hemophilia A is caused by a factor VIII deficiency, while patients with hemophilia B are deficient in FIX.

In 2018, the U.S. Food and Drug Administration approval of emicizumab revolutionized treatment for patients with hemophilia A. Emicizumab is a prophylaxis treatment that mimics the coagulation function of missing factor VIII. Since the antibody lasts long in the body, patients only need injections twice per month, rather than multiple times per week, and the treatment can be given through the skin, rather than directly into a vein. By contrast, patients diagnosed with hemophilia B must rely on regular, intravenous infusions of FIX.

Their preclinical findings were published in Blood. Read more in this CHOP press release.

ICYMI

Catch up on our headlines from our Nov. 8 In The News:

• Serum Cytokine Panels Inform Patient Management in Real Time
• Early Research Shows mRNA Vaccine Treats, Prevents C. diff in Disease Models
• Lifespan Brain Institute's Annual Symposium Spotlights 'Pathways to Psychosis'
• Study Reveals CRISPR/Cas9 Genome Editing Mechanics
• New Grant to Promote Secure Firearm Storage Interventions
• Identifying Healthcare Point of Entry Could Improve Concussion Recovery

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