ESPE Abstracts

Background: There is increasing evidence from epidemiological studies that some man-made chemicals present in the environment can disrupt endocrine homeostasis in exposed humans. Exposure during foetal life to e.g. phthalates has been linked to adverse effects on testicular and ovarian development, thyroid homeostasis and growth in postnatal life. Exposure to phthalates fluctuates not only from day to day but also over time which poses a major challenge for ex...

Background: The process of sexual differentiation is critical for reproduction in nearly all metazoan. Defects in any of the genes involved in either testicular or ovarian development can result in disorders of sex development (DSD). CBX2/M33 is a chromatin modifier that plays an important role in sexual development and its disorders, highlighted by the fact that M33-deficient mice have male-to-female sex reversal and loss-of-function of CBX2 causes 46, XY DSD...

Background: The process of sexual differentiation is critical for reproduction in nearly all metazoan. Defects in any of the genes involved in either testicular or ovarian development can result in disorders of sex development (DSD). CBX2/M33 is a chromatin modifier that plays an important role in sexual development and its disorders, highlighted by the fact that M33-deficient mice have male-to-female sex reversal and loss-of-function of CBX2 causes 46, XY DSD in humans. Human...

Background: Congenital Hyperinsulinism(CHI) is characterized by the unregulated secretion of insulin in the presence of hypoglycaemia. The mutations in ABCC8 and KCNJ11, which encode the sulfonylurea receptor 1 (SUR1) and potassium inward-rectifying 6.2 (Kir6.2) subunits of ATP-sensitive potassium channel (K channel), are the most common identified cause of the condition. Defects in the HADH gene are responsible for SCHAD- HI, a rare form of the disease caused...

Background: Beta-tumour cells (βTC) are a group of highly differentiated beta cell lines derived by expression of the SV40 T antigen (Tag) oncoprotein under control of the insulin promoter in transgenic mice. βTC-6 cells exhibit glucose stimulated insulin secretion which makes them a valuable tool in understanding the mechanisms that regulate insulin secretion.The CRISPR/Cas9 genome-editing platform is a versatile and pow...

Background: Congenital Hyperinsulinism(CHI) is characterized by the unregulated secretion of insulin in the presence of hypoglycaemia. The mutations in ABCC8 and KCNJ11, which encode the sulfonylurea receptor 1 (SUR1) and potassium inward-rectifying 6.2 (Kir6.2) subunits of ATP-sensitive potassium channel (K channel), are the most common identified cause of the condition. Defects in the HADH gene are responsible for SCHAD- HI, a rare form of the disease caused by the disruptio...

Background: CTP-modified hGH (MOD-4023) has been developed for once weekly administration in GH deficient (GHD) adults and children. Immunogenicity samples of once-weekly s.c. administration of MOD-4023 were detected for the presence of binding and neutralizing anti-MOD-4023 Ab’s in pediatric Phase 2 study.Objective and hypotheses: During the first year of the study, 53 pre-pubertal GHD children were treated with once-weekly s.c. injections of one o...

Background: Poland syndrome (PS) is characterized by unilateral absence or hypoplasia of the pectoralis muscle, most frequently involving the sternocostal portion of the pectoralis major muscle, and a variable degree of ipsilateral hand and digit anomalies, including symbrachydactyly. Congenital Hyperinsulinism (CHI) is the result of unregulated insulin secretion from the pancreatic β-cells leading to severe hypoglycaemia. We report a baby with Poland’s syndrome and ...

Background: OPKO Biologics is developing MOD-4023, a long-acting growth hormone (GH), intended for weekly dosing for the treatment of idiopathic GH deficiency in children. At ESPE2015, we presented pharmacokinetic (PK) and pharmacodynamic (PD, based on IGF-1) models for weekly MOD-4023 administration in children aged 3–11 years. These models confirm that IGF-1 (and IGF-1 SDS) varies during the dosing interval. One critical clinical and research issue is when to optimally ...

Background: OPKO Biologics is developing MOD-4023, a long-acting growth hormone (GH), intended for weekly dosing for the treatment of idiopathic GH deficiency in children. At ESPE2015, we presented pharmacokinetic (PK) and pharmacodynamic (PD, based on IGF-1) models for weekly MOD-4023 administration in children aged 3–11 years. Those models were based on data collected during the ‘PKPD period’ (the second steady state dose of MOD-4023) and monthly values during...