Gabriela Ullio-Gamboa1, Kenea C Udobi2, Sophie Dezard3, Marla K Perna2, Keila N Miles2, Narciso Costa1, Frédéric Taran3, Alain Pruvost4, Jean-Pierre Benoit5, Matthew R Skelton2, Pascale de Lonlay6, Aloïse Mabondzo1. 1. Service de Pharmacologie et d'Immunoanalyse, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France. 2. Department of Pediatrics, University of Cincinnati College of Medicine & Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, USA. 3. Service de Chimie Bio Organique et de Marquage CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France. 4. Service de Pharmacologie et d'Immunoanalyse (SPI), Plateforme Smart-MS, CEA, INRA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France. 5. LUNAM Université-Micro et Nanomédecines Biomimétiques, F-49933 Angers, France, INSERM U1066, IBS-CHU, 4 rue Larrey, F-49933 Angers Cedex 9, France. 6. Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte, Hôpital Necker-Enfants Malades, APHP, Université Paris Descartes, Imagine, INEM, Filière G2M, metabERN, Paris, France.
Abstract
Creatine transporter (CrT) deficiency is an X-linked intellectual disability caused by mutations of CrT. Aim: This work focus on the preclinical development of a new therapeutic approach based on a microemulsion (ME) as drug delivery system for dodecyl creatine ester (DCE). Materials & methods: DCE-ME was prepared by titration method. Novel object recognition (NOR) tests were performed before and after DCE-ME treatment on Slc6a8-/y mice. Results: Intranasal administration with DCE-ME improved NOR performance in Slc6a8-/y mice. Slc6a8-/y mice treated with DCE-ME had increased striatal ATP levels mainly in the striatum compared with vehicle-treated Slc6a8-/y mice which was associated with increased expression of synaptic markers. Conclusion: These results highlight the potential value of DCE-ME as promising therapy for creatine transporter deficiency.
Creatine transporter (CrT) deficiency is an X-linked intellectual disability caused by mutations of CrT. Aim: This work focus on the preclinical development of a new therapeutic approach based on a microemulsion (ME) as drug delivery system for dodecyl creatine ester (DCE). Materials & methods: DCE-ME was prepared by titration method. Novel object recognition (NOR) tests were performed before and after DCE-ME treatment on Slc6a8-/y mice. Results: Intranasal administration with DCE-ME improved NOR performance in Slc6a8-/y mice. Slc6a8-/y mice treated with DCE-ME had increased striatal ATP levels mainly in the striatum compared with vehicle-treated Slc6a8-/y mice which was associated with increased expression of synaptic markers. Conclusion: These results highlight the potential value of DCE-ME as promising therapy for creatine transporter deficiency.
Entities:
Keywords:
creatine; creatine transporter deficiency; dodecyl creatine ester; drug delivery; microemulsion; nasal administration; neurotherapeutics for CTD
Authors: Margaret Fahnestock; Monica Marchese; Elizabeth Head; Viorela Pop; Bernadeta Michalski; William N Milgram; Carl W Cotman Journal: Neurobiol Aging Date: 2010-05-05 Impact factor: 4.673
Authors: Matthew F Muldoon; Christopher M Ryan; Lei Sheu; Jeffrey K Yao; Sarah M Conklin; Stephen B Manuck Journal: J Nutr Date: 2010-02-24 Impact factor: 4.798
Authors: Yuko Kurosawa; Ton J Degrauw; Diana M Lindquist; Victor M Blanco; Gail J Pyne-Geithman; Takiko Daikoku; James B Chambers; Stephen C Benoit; Joseph F Clark Journal: J Clin Invest Date: 2012-07-02 Impact factor: 14.808
Authors: K C Udobi; A N Kokenge; E R Hautman; G Ullio; J Coene; M T Williams; C V Vorhees; A Mabondzo; M R Skelton Journal: Genes Brain Behav Date: 2018-02-20 Impact factor: 3.449
Authors: Alexandra Trotier-Faurion; Sophie Dézard; Frédéric Taran; Vassili Valayannopoulos; Pascale de Lonlay; Aloïse Mabondzo Journal: J Med Chem Date: 2013-06-07 Impact factor: 7.446
Authors: Elsa Ghirardini; Francesco Calugi; Giulia Sagona; Federica Di Vetta; Martina Palma; Roberta Battini; Giovanni Cioni; Tommaso Pizzorusso; Laura Baroncelli Journal: Genes (Basel) Date: 2021-07-24 Impact factor: 4.096
Authors: Zuhair I Abdulla; Bahar Pahlevani; Kerstin H Lundgren; Jordan L Pennington; Kenea C Udobi; Kim B Seroogy; Matthew R Skelton Journal: J Mol Neurosci Date: 2019-09-13 Impact factor: 3.444
Authors: Francesco Cacciante; Mariangela Gennaro; Giulia Sagona; Raffaele Mazziotti; Leonardo Lupori; Elisa Cerri; Elena Putignano; Mark Butt; Minh-Ha T Do; John C McKew; Maria Grazia Alessandrì; Roberta Battini; Giovanni Cioni; Tommaso Pizzorusso; Laura Baroncelli Journal: Sci Rep Date: 2020-10-27 Impact factor: 4.379
Authors: Hong-Ru Chen; Xiaohui Zhang-Brotzge; Yury M Morozov; Yuancheng Li; Siming Wang; Helen Heju Zhang; Irena S Kuan; Elizabeth M Fugate; Hui Mao; Yu-Yo Sun; Pasko Rakic; Diana M Lindquist; Ton DeGrauw; Chia-Yi Kuan Journal: JCI Insight Date: 2021-09-08