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IGF-1 as a Drug for Preterm Infants : A Step-Wise Clinical Development

Hellstrom, Ann ; Ley, David LU ; Hallberg, Boubou ; Lofqvist, Chatarina ; Hansen-Pupp, Ingrid LU orcid ; Ramenghi, Luca A ; Borg, Jan ; Smith, Lois E H and Hard, Anna-Lena (2017) In Current Pharmaceutical Design 23(38). p.5964-5970
Abstract

BACKGROUND: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm... (More)

BACKGROUND: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants.

METHODS: In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 µg/kg), that increased serum IGF-1 to levels close to those observed in fetuses and preterm infants of similar GAs. Thereafter, a Phase I 3 hours IV infusion of rhIGF-1/rhIGFBP-3 was conducted in 5 infants, followed by a Phase II study with four sections (A-D). In the Phase II, sections A-D studies, time on infusion increased and younger gestational ages were included.

RESULTS: IV infusion increased IGF-1 but with short half-life (0.5h) implying a need for continuous infusion. In order to obtain in utero levels of IGF-I, the dose was increased from 100 to 250 µg/kg/24 h and the infusion was prolonged from 3 weeks postnatal age until a postmenstrual age of 29 weeks and 6 days.

CONCLUSION: The purpose has been to ensure high-quality research into the development of a new drug for preterm infants. We hope that our work will help to establish a new standard for the testing of medications for preterm infants.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Drug Development/methods, Humans, Infant, Newborn, Infusions, Intravenous, Insulin-Like Growth Factor I/administration & dosage, Plasma/metabolism
in
Current Pharmaceutical Design
volume
23
issue
38
pages
7 pages
publisher
Bentham Science Publishers
external identifiers
  • pmid:28969546
  • scopus:85036548393
ISSN
1381-6128
DOI
10.2174/1381612823666171002114545
language
English
LU publication?
yes
additional info
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
id
344ad69c-2159-4e2f-9a97-3de290171fa6
date added to LUP
2021-02-15 18:45:34
date last changed
2024-06-14 11:37:24
@article{344ad69c-2159-4e2f-9a97-3de290171fa6,
  abstract     = {{<p>BACKGROUND: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants.</p><p>METHODS: In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 µg/kg), that increased serum IGF-1 to levels close to those observed in fetuses and preterm infants of similar GAs. Thereafter, a Phase I 3 hours IV infusion of rhIGF-1/rhIGFBP-3 was conducted in 5 infants, followed by a Phase II study with four sections (A-D). In the Phase II, sections A-D studies, time on infusion increased and younger gestational ages were included.</p><p>RESULTS: IV infusion increased IGF-1 but with short half-life (0.5h) implying a need for continuous infusion. In order to obtain in utero levels of IGF-I, the dose was increased from 100 to 250 µg/kg/24 h and the infusion was prolonged from 3 weeks postnatal age until a postmenstrual age of 29 weeks and 6 days.</p><p>CONCLUSION: The purpose has been to ensure high-quality research into the development of a new drug for preterm infants. We hope that our work will help to establish a new standard for the testing of medications for preterm infants.</p>}},
  author       = {{Hellstrom, Ann and Ley, David and Hallberg, Boubou and Lofqvist, Chatarina and Hansen-Pupp, Ingrid and Ramenghi, Luca A and Borg, Jan and Smith, Lois E H and Hard, Anna-Lena}},
  issn         = {{1381-6128}},
  keywords     = {{Drug Development/methods; Humans; Infant, Newborn; Infusions, Intravenous; Insulin-Like Growth Factor I/administration & dosage; Plasma/metabolism}},
  language     = {{eng}},
  number       = {{38}},
  pages        = {{5964--5970}},
  publisher    = {{Bentham Science Publishers}},
  series       = {{Current Pharmaceutical Design}},
  title        = {{IGF-1 as a Drug for Preterm Infants : A Step-Wise Clinical Development}},
  url          = {{http://dx.doi.org/10.2174/1381612823666171002114545}},
  doi          = {{10.2174/1381612823666171002114545}},
  volume       = {{23}},
  year         = {{2017}},
}