Maïthé Tauber1,2,3, Kader Boulanouar4, Gwenaelle Diene5,6, Sophie Çabal-Berthoumieu5,7, Virginie Ehlinger6, Pascale Fichaux-Bourin5, Catherine Molinas5,2,3, Sandy Faye5,2, Marion Valette5,2, Jeanne Pourrinet5, Catie Cessans5, Sylvie Viaux-Sauvelon8, Céline Bascoul7, Antoine Guedeney9, Patric Delhanty10, Vincent Geenen11, Henri Martens11, Françoise Muscatelli12, David Cohen8,13, Angèle Consoli8,14, Pierre Payoux4, Catherine Arnaud6,15, Jean-Pierre Salles5,2,3. 1. Unité d'Endocrinologie, Obésité, Maladies Osseuses, Génétique et Gynécologie Médicale. Centre de Référence du Syndrome de Prader-Willi, tauber.mt@chu-toulouse.fr. 2. Axe Pédiatrique du Centre d'Investigation Clinique 9302/Intitut National de la Santé Et de la Recherche Médicale, and. 3. Institut National de la Santé Et de la Recherche Médicale Unité 1043, Centre de Physiopathologie de Toulouse Purpan, Université Paul Sabatier, Toulouse, France. 4. Toulouse NeuroImaging Center, Université de Toulouse, Institut National de la Santé Et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France. 5. Unité d'Endocrinologie, Obésité, Maladies Osseuses, Génétique et Gynécologie Médicale. Centre de Référence du Syndrome de Prader-Willi. 6. Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1027, Université Toulouse III, Hôpital Paule de Viguier, Toulouse, France. 7. Service de Psychiatrie de l'Enfant et de l'Adolescent, Hôpital des Enfants, Toulouse, France. 8. Service de Psychiatrie de l'Enfant et de l'Adolescent, la Pitié Salpêtrière, Paris, France. 9. Service de Psychiatrie de l'Enfant et de l'Adolescent, Hôpital Bichat-Claude Bernard, Paris, France. 10. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands. 11. Grappe Interdisciplinaire de Génoprotéomique Appliquée-I3-Immunoendocrinologie, Université de Liège, Sart Tilman, Liege, Belgium. 12. Institut de Neurobiologie de la Méditerranée, Institut de la Santé Et de la Recherche Médicale Unité 901, Marseille, France. 13. Centre National de la Recherche Sscientifique, Unité Mixte de Recherche 7222, Institut des Systèmes Intelligents et de Robotiques, and. 14. Groupe de Recherches Cliniques Abord dimensionnel des épisodes psychotiques de l'enfant et de l'adolescent, Université Pierre et Marie Curie, Paris France; and. 15. Unité de Soutien méthodologique à la recherche, CHU Toulouse, Toulouse, France.
Abstract
BACKGROUND AND OBJECTIVES: Patients with Prader-Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively. Significant improvements in Clinical Global Impression scale scores, social withdrawal behavior, and mother-infant interactions were observed. We documented a significant increase in acylated ghrelin and connectivity of the right superior orbitofrontal network that correlated with changes in sucking and behavior. CONCLUSIONS: OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems.
BACKGROUND AND OBJECTIVES:Patients with Prader-Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively. Significant improvements in Clinical Global Impression scale scores, social withdrawal behavior, and mother-infant interactions were observed. We documented a significant increase in acylated ghrelin and connectivity of the right superior orbitofrontal network that correlated with changes in sucking and behavior. CONCLUSIONS:OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems.
Authors: Marilena M DeMayo; Larry J Young; Ian B Hickie; Yun Ju C Song; Adam J Guastella Journal: Neurosci Biobehav Rev Date: 2019-09-24 Impact factor: 8.989
Authors: Juan A Rodriguez; Emily C Bruggeman; Bharath K Mani; Sherri Osborne-Lawrence; Caleb C Lord; Henry F Roseman; Hannah L Viroslav; Prasanna Vijayaraghavan; Nathan P Metzger; Deepali Gupta; Kripa Shankar; Claudio Pietra; Chen Liu; Jeffrey M Zigman Journal: Endocrinology Date: 2018-12-01 Impact factor: 4.736