The Manne Research Institute provided COVID-19 Springboard Exploratory Research Awards to seven researchers to better understand aspects of COVID-19 from a pediatric perspective. As the pandemic developed, little was known about how the virus spreads or how it damages the body. These seed grants are being used to ultimately help reveal better treatment and prevention strategies for young patients. They also support investigators' work to identify how the pandemic exacerbated health disparities and access to care and to develop solutions to these problems. Studies from several researchers have already been published. One, by infectious disease specialist Taylor Heald-Sargent, MD, PhD, has important implications for the reopening of schools and daycare centers. Her landmark study featured in JAMA Pediatrics found that children under 5 with COVID-19 have a higher viral load than older children and adults, which may suggest greater transmission.
year-over-year increase in external funding
Following clinical trials at the Manne Research Institute and other institutions, the FDA approved Palforzia earlier this year to mitigate reactions to peanuts in patients ages 4-17. Palforzia is a milestone: the first approved therapy to desensitize children to peanuts and reduce the risk of severe reaction in case patients accidentally eat the food. Palforzia is an oral immunotherapy powder that patients ingest under close supervision to build tolerance to the food. Jacqueline Pongracic, MD, Head of the Division of Allergy & Immunology, was principal investigator of the drug trial for Lurie Children’s. Peanut allergy affects approximately 1 million children in the U.S and only 20 percent will ever outgrow this food allergy.
A cell-signaling protein called tumor necrosis factor (TNF) may make medulloblastoma tumors—the most common malignant brain tumors in children—more susceptible to treatment and decrease side effects from cancer therapy. Surgery, radiation and chemotherapy can improve patient outcomes, but many children remain incurable and survivors often suffer severe side effects from treatment, including long-term damage to the brain and endocrine system. A therapeutic approach integrating TNF has the potential to improve quality of life and reduce treatment toxicity for young patients. Xiao-Nan Li, MD, PhD, at the Manne Research Institute, and pediatric oncologist Oren Becher, MD, published their significant advance in understanding this cancer in the prominent journal Nature Neuroscience.
Pediatric infectious disease expert Anne Rowley, MD, is at the forefront of global efforts to solve why Kawasaki Disease (KD) occurs and develop effective therapies. An estimated 4,500 children annually are diagnosed in the U.S. with KD, the leading cause of acquired heart disease in childhood. Dr. Rowley’s lab at the Manne Research Institute was the first to identify a portion of the protein sequence that is targeted by the antibodies that children with KD produce as part of their immune response—thus pinpointing what the exact viral cause(s) may be. This initial discovery was published in the Journal of Infectious Diseases, and Dr. Rowley continues to map out the entire protein sequence, which will make effective treatment and prevention strategies possible.
The drug luspatercept has shown to reduce the need for blood transfusions in patients with transfusion-dependent beta-thalassemia. The New England Journal of Medicine published this phase III clinical trial work co-authored by Alexis Thompson, MD, MPH, Head of Hematology and Director of the Comprehensive Thalassemia Program, which could be life-changing for patients with severe cases of the disease. The drug, FDA-approved for adults in 2019, is the first disease-modifying therapy for thalassemia. Patients with severe cases of beta-thalassemia are profoundly anemic and require regular, lifelong blood transfusions. With luspatercept, patients required less blood during transfusions, which could reduce complications and lessen demand on the healthcare system for blood supplies.
The genetic basis for Armfield XLID syndrome, a rare intellectual disability, has been identified and is opening the door to better diagnostics and treatments for similar diseases of the nervous system. Erica Davis, PhD, of the Manne Research Institute’s Advanced Center for Translational and Genetic Medicine, discovered the specific gene and underlying process responsible. Published in Nature Communications, she pinpoints that mutations in the FAM5OA gene cause defects in the gene-splicing process, and the cell protein production process goes awry. Armfield XLID syndrome is characterized by impaired growth and causes dysmorphic facial features and seizures. This finding, along with other recent studies, shows a rising class of diseases called “spliceosomopathies” that interfere with neurodevelopment.