Review
Version 1
Preserved in Portico This version is not peer-reviewed
PPAR Gamma Receptor: A Novel Target to Improve Morbidity in Preterm Babies
Version 1
: Received: 31 August 2023 / Approved: 31 August 2023 / Online: 1 September 2023 (13:47:05 CEST)
A peer-reviewed article of this Preprint also exists.
Victor, S.; Forbes, B.; Greenough, A.; Edwards, A.D. PPAR Gamma Receptor: A Novel Target to Improve Morbidity in Preterm Babies. Pharmaceuticals 2023, 16, 1530. Victor, S.; Forbes, B.; Greenough, A.; Edwards, A.D. PPAR Gamma Receptor: A Novel Target to Improve Morbidity in Preterm Babies. Pharmaceuticals 2023, 16, 1530.
Abstract
Three-quarters of a million babies are born extremely preterm (< 28 weeks’ gestation) world-wide with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopul-monary dysplasia (BPD) and 10% suffer from cerebral palsy.
Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal pe-riod.
In newborn animal models, pioglitazone is shown to be protective against BPD, necrotising en-terocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelop-ment.
Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema seen rarely in adults may be avoided with a short treatment course. Other effects of pioglitazone including improved glycaemic control and lipid metabolism may provide added benefit in prematurity.
Currently, there is no formulation of pioglitazone suited for administration to preterm babies A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns.
Keywords
pioglitazone; prematurity; Bronchopulmonary dysplasia; lung, brain; adiponectin; PPAR gamma
Subject
Medicine and Pharmacology, Pediatrics, Perinatology and Child Health
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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