ESPE Abstracts

Background: GH insensitivity is caused by disturbances of GH receptor function or inability to transduce the hormone signal. Affected children are severely growth retarded and may also present immune complications when the transducer STAT5B is defective. Only autosomal-recessive STAT5B mutations have been described to date.Clinical case: Two male 14.5 year monozygotic twins presented with heights of 131.5 cm (−5.3 SDS). Bone age of the ind...

Background: Daily injections are currently required for growth hormone (GH) replacement therapy, which may cause poor compliance, inconvenience and distress for patients. MOD-4023 is a CTP-modified human GH (hGH) developed for once-weekly administration in growth hormone deficient (GHD) adults and children.Objective and hypotheses: In the present Phase 2 study, the safety and tolerability of once-weekly subcutaneous (SC) administration of MOD-4023 were a...

Background: Growth hormone (GH) replacement therapy currently requires daily injections, which may cause poor compliance, inconvenience and distress for patients. CTP-modified hGH (MOD-4023) has been developed by OPKO Biologics for once-weekly administration in growth hormone-deficient (GHD) adults and children.Objective and hypotheses: The 24-month efficacy of once-weekly subcutaneous (SC) administration of MOD-4023 was evaluated in a Phase 2 study in G...

Background: Once-daily growth hormone (GH) therapy is an effective treatment for children with growth hormone deficiency (GHD), but compliance wanes with ongoing treatment. A once -weekly GH, somatrogon (hGH-CTP), is being developed to reduce the treatment burden of daily dosing for children and caregivers and potentially improve compliance and long-term efficacy. The impact of once-weekly somatrogon on long-term safety, local tolerability and immunogenicity w...

Background: TV-1106 (Teva Pharmaceuticals) is a genetically fused human GH and human serum albumin, in development for treatment of GH deficiency (GHD). TV-1106 has an extended duration of action compared to daily GH treatment and thus it is believed that treatment with TV-1106 can reduce the frequency of injections and improve compliance and quality of life for those requiring growth hormone replacement therapy. The efficacy and safety data from adult studies with TV-1106 sup...

Background: Heterozygous mutations in the IGF1 receptor (IGF1R) are often associated with congenital IGF1 resistance, causing variable degrees of intrauterine growth retardation (IUGR) and postnatal short stature. To date, only one homozygous IGF1R mutation has been reported, in a child presenting with severe growth failure, mild intellectual impairment, microcephaly, dysmorphic features, and cardiac malformations.Objective: We now repo...

Background: PAPP-A2 is a metalloproteinase that specifically cleaves IGFBPs 3 and 5. Papp-a2 knock-out (KO) mice show a reduction in body size and skeletal abnormalities.Objective and hypotheses: Our objective is to report two affected families from Spain and USA. The Spanish family presents a homozygous frameshift mutation in exon 3 of the PAPP-A2 gene (c.1927_ 1928insAT, p.D643fs25X) resulting in a premature stop codon, with 2 of 4 si...

There are few issues in pediatric endocrinology which have generated as much controversy as that of GH treatment of ISS. The genesis of this debate is totally understandable, given that ISS is not a ‘disease,’ but, rather, a heterogeneous collection of conditions that are defined auxologically as a height below −2 S.D., without evidence of an underlying systemic, nutritional, endocrine or chromosomal disorder. One can quite rightfully state that ...

Background: IGFALS deficiency is a rare cause of GH insensitivity (GHI). We report a German girl with short stature who was born as 2nd child at 40 weeks of gestation. Her Caucasian parents were unrelated and healthy (target height 168 cm, SDS 0.2). She was born appropriately sized for gestational age (49 cm, SDS -1.2; 2950 g, SDS-1.2). Height (104.8 cm; SDS -2.94) and height velocity (5.1 cm / year; SDS -1.67) were reduced at the age of 6 years.</p...

Objective: GH replacement therapy currently requires daily injections, which may cause poor compliance, inconvenience and distress for patients. CTP-modified hGH (MOD-4023) has been developed for once-weekly administration in GH deficient (GHD) adults and children. Pharmacokinetics (PK), pharmacodynamics, (PD) efficacy and safety analysis of weekly treatment with MOD-4023 in GHD naïve children was performed and compared to daily hGH.Design and metho...