Novel research and innovation inform clinical practice across multiple specialties

Diabetes & Endocrinology

Novel T1D study underway

Riley endocrinologists and diabetes researchers at IU School of Medicine are leading a clinical trial investigating difluoromethylornithine (DFMO) as a disease-modifying therapy for Type 1 diabetes (T1D). The TADPOL (Targeting Type 1 Diabetes via Polyamines) study evaluates whether DFMO can improve beta cell health for people with T1D.

“TADPOL is novel because it’s testing a drug that potentially makes the beta cell healthier versus targeting the immune system,” explained Emily K. Sims, MD, who with Riley colleague Linda DiMeglio, MD, MPH, published the results of a pilot study highlighting DFMO’s role in preserving beta cell function in T1D.

Riley contributes to groundbreaking T1D therapy

A clinical trial site for therapies designed to modify the course of T1D, Riley Children’s participated in a study examining the safety and efficacy of the breakthrough therapy teplizumab in children living with early-stage disease. Leaders in the original TrialNet teplizumab study, Riley endocrinologists co-authored the Pediatric Endocrine Society’s clinical practice considerations for using teplizumab.

Nephrology

Research reveals new treatment options for VUR and UTI

Riley nephrologists have uncovered new findings about kidney damage in children with vesicoureteral reflux (VUR). Challenging a decades-old standard, the research team discovered that a commonly used test to evaluate the impact of recurrent urinary tract infections (UTIs) on the kidneys may not be the best method.

“We’ve found that kids with VUR and UTIs have more genetic variations in urinary tract protection genes, which could be a possible source of their UTIs,” said Riley nephrology division chief David Hains, MD, MBA, who also serves as vice chair of the American Academy of Pediatrics UTI clinical practice guidelines committee.

Integrating patient visits and research drives new therapies

Targeting glomerular diseases, Riley nephrologists Myda Khalid, MD, and Andrew Schwaderer, MD, lead BRIDGE (Biorepository, Registry, Integrated Clinic, Biomarker Discovery and Glomerular Disease Exploration), a unique program integrating clinic visits and research. The approach improves access to expert care, facilitates crucial biomarker discovery and enhances recruitment for pediatric clinical trials.

Pulmonology

Clinical research addresses cystic fibrosis (CF) care

As one of the few U.S. pediatric centers to offer theratyping, Riley Children’s has helped patients gain access to highly effective CF transmembrane conductance regulator (CFTR) modulators. Riley physician-scientists have shown efficacy of CFTR modulators in patients without a qualifying mutation.

“We've discovered that some patients who possess mutations we thought were not responsive to modulators actually do respond to these medications in nasal epithelial cell theratyping studies,” said Don B. Sanders, MD, MS.

Researchers pursue personalized therapies for severe asthma

Leading a $12 million program project grant (P01), Benjamin Gaston, MD, is exploring three projects related to severe asthma: S-nitrosylation signaling, airway pH regulation and androgen signaling. These mechanisms are not only indicators of the type of severe asthma a person has, but also potential targets for personalized treatment.

Neonatology

rGS promotes more targeted treatment for NICU patients

Riley specialists are using rapid genome sequencing (rGS) to detect genetic disease in hospitalized infants in the neonatal intensive care unit (NICU). Kristen Suhrie, MD, medical director of the first perinatal genomics program of its kind in the U.S., and Riley colleagues have developed a new NICU genetic evaluation algorithm that has created a paradigm shift in current practice across Riley NICUs.

“We feel it’s important not only for newborns at Riley to get this type of care, but for this to be implemented in NICUs across the country,” Dr. Suhrie explained.

Gastroenterology

Pediatric liver disease cell models provide insights for new therapies

To understand the biology of pediatric metabolic dysfunction-associated steatohepatitis (MASH), Brian DeBosch, MD, PhD, co-division chief of Riley gastroenterology, is developing bioengineered liver organoids, mini models of pediatric liver disease, using innovative technology developed by a research partner at Purdue University. The organoids are engineered to give the best glimpse into what makes pediatric MASH unique and provide new insights to develop much-needed therapies. The research team may be among the first in the U.S. to use organoid technology to create cell models of pediatric liver disease for study in a culture dish.

“We must go beyond the common advice for patients to simply ‘eat less,’ to making better, more intentional recommendations rooted in a deeper, scientifically proven understanding of what contributes to MASH in children,” Dr. DeBosch said.