Service de Pharmacologie et d'Immunoanalyse, CEA, Université Paris-Saclay, F-91191 Gif-sur-Yvette, France.
Department of Pediatrics, University of Cincinnati College of Medicine & Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, USA.
Nanomedicine (Lond). 2019 Jun;14(12):1579-1593. doi: 10.2217/nnm-2019-0059. Epub 2019 Apr 30.
Creatine transporter (CrT) deficiency is an X-linked intellectual disability caused by mutations of CrT. 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). DCE-ME was prepared by titration method. Novel object recognition (NOR) tests were performed before and after DCE-ME treatment on mice. Intranasal administration with DCE-ME improved NOR performance in mice. mice treated with DCE-ME had increased striatal ATP levels mainly in the striatum compared with vehicle-treated mice which was associated with increased expression of synaptic markers. These results highlight the potential value of DCE-ME as promising therapy for creatine transporter deficiency.
肌酸转运蛋白 (CrT) 缺乏症是一种由 CrT 突变引起的 X 连锁智力障碍。本工作专注于一种新治疗方法的临床前开发，该方法基于微乳液 (ME) 作为十二烷基肌酸酯 (DCE) 的药物递送系统。通过滴定法制备 DCE-ME。在给予 DCE-ME 前后，对小鼠进行新物体识别 (NOR) 测试。DCE-ME 的鼻内给药改善了小鼠的 NOR 表现。与给予载体的 小鼠相比，用 DCE-ME 治疗的 小鼠纹状体中的 ATP 水平升高，主要是在纹状体中，这与突触标记物的表达增加有关。这些结果突出了 DCE-ME 作为肌酸转运蛋白缺乏症有希望的治疗方法的潜在价值。
