hrp0094p2-235 | Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) | ESPE2021

A Selective Nonpeptide Somatostatin Receptor 5 (SST5) Agonist Effectively Decreases Insulin Secretion in a KATPHI Mouse Model and in Human HI Islets

Juliana Christine , Chai Jinghua , Arroyo Pablo , Rico-Bautista Elizabeth , Betz Stephen , De Leon Diva ,

Inactivating mutations of ß-cell KATP channels cause the most common and severe form of congenital hyperinsulinism (HI), a ß-cell disorder that results in dysregulated insulin secretion and persistent hypoglycemia. Children with KATPHI are typically unresponsive to diazoxide, the only FDA-approved drug for HI. Octreotide, an SST2-selective agonist peptide that inhibits insulin secretion, is used as second line therapy, but poor efficacy and SST2...

hrp0095fc11.4 | Late Breaking | ESPE2022

CRN04777, an oral, nonpeptide selective SST5 receptor agonist, dose-dependently suppresses both fasting and stimulated insulin secretion: results from a first in human study

Ferrara-Cook Christine , Luo Rosa , De la Torre Eduardo , Wang Yang , Betz Stephen , Lagast Hjalmar , Struthers Scott , Hovelmann Ultike , Heise Tim , Krasner Alan

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in neonates, infants, and children, and is caused by genetic mutations in pancreatic beta-cells. Current therapies are burdensome, have limited efficacy, and are associated with significant morbidity. CRN04777 is a potent, orally-bioavailable, selective SST5 agonist that suppresses insulin secretion in the terminal steps of the insulin secretion pathway and could be useful for patients with con...

hrp0097p1-279 | Fetal, Neonatal Endocrinology and Metabolism | ESPE2023

A Year-Long, National Trial of Prospective CGM Use in Families with Hyperinsulinism

Worth Chris , Worthington Sarah , Auckburally Sameera , Ahmad Sumera , O'Shea Elaine , Ferrera-Cook Chris , F Betz Stephen , Salomon-Estebanez Maria , Banerjee Indraneel

Introduction: Congenital hyperinsulinism (CHI) is the commonest cause of severe hypoglycaemia in early childhood but glycaemic characterisation remains scarce. Continuous glucose monitoring (CGM) offers a deep understanding of glycaemic control to understand disease burden, individualise patient care and inform therapeutic trials in CHI. Preliminary studies suggest inadequate accuracy and no efficacy of standalone CGM to reduce hypoglycaemia. Provision is hist...

hrp0094p2-126 | Diabetes and insulin | ESPE2021

Oral administration of CRN04777, a nonpeptide selective SST5 receptor agonist, suppresses insulin secretion and rescues hypoglycemia in neonatal rat models of congenital hyperinsulinism

Fowler Melissa , Zhao Jian , Sturchler Emmanuel , Athanacio Jon , Kredel Taylor , Antwan Agnes , Yan Claudia , Staley Christine , Chen Jenny , Kusnetzow Ana Karin , Struthers R. Scott , Zhu Yun Fei , Betz Stephen , Markison Stacy ,

CRN04777 is an orally administered nonpeptide that is a potent and selective agonist of somatostatin 5 (SST5) receptors and is currently under development for the treatment of congenital hyperinsulinism (HI), the most common cause of persistent hypoglycemia in newborns and infants. Congenital HI arises from mutations within the insulin secretion pathway and is characterized by excessive and/or inappropriate insulin secretion by pancreatic islet beta cells. This excess insulin ...