Department of Child Neurology, Hospital Universitari Sant Joan de Déu, Centre for Research on Rare Diseases, CIBERER, Barcelona, Spain.
Mol Genet Metab. 2010 Mar;99(3):296-9. doi: 10.1016/j.ymgme.2009.10.186. Epub 2009 Nov 1.
Creatine transporter (CRTR) deficiency is one of the most frequent causes of X-linked mental retardation. The lack of an effective treatment for this disease, in contrast to creatine (Cr) biosynthesis disorders that respond to Cr monohydrate (CM), led us to analyze the efficacy of a lipophilic molecule derived from Cr, creatine ethyl ester (CEE), in fibroblasts and patients with CRTR deficiency. CM and CEE uptake studies were performed in six controls and four fibroblast cell lines from patients. We found a significant increase in Cr uptake after 72 h of incubation with CEE (500 micromol/L) in patients and control fibroblasts compared to incubation with CM. Subsequently, we assayed the clinical effect of CEE administration in four patients with CRTR deficiency. After 1 year of treatment, a lack of significant improvement in neuropsychological assessment or changes in Cr level in brain (1)H MRS was observed, and CEE was discontinued. In conclusion, this 12-month trial with CEE did not increase the brain concentration of Cr. Our in vitro data lend support to the idea of a certain passive transport of CEE in both pathological and control cells, although more lipophilic molecules or other cell systems that mimic the BBB should be used for a better approach to the in vivo system.
肌酸转运蛋白（CRTR）缺陷是最常见的 X 连锁智力低下的原因之一。与对肌酸一水合物（CM）有反应的肌酸（Cr）生物合成障碍不同，这种疾病缺乏有效的治疗方法，这促使我们分析了一种源自 Cr 的亲脂分子肌酸乙酯（CEE）在 CRTR 缺陷的成纤维细胞和患者中的疗效。在 6 名对照和 4 名来自患者的成纤维细胞系中进行了 CM 和 CEE 摄取研究。与用 CM 孵育相比，我们发现患者和对照成纤维细胞在用 CEE（500 μmol/L）孵育 72 小时后 Cr 摄取显著增加。随后，我们在 4 名 CRTR 缺陷患者中检测了 CEE 给药的临床效果。经过 1 年的治疗，观察到神经心理学评估缺乏明显改善，脑部（1）H MRS 中 Cr 水平也没有变化，因此停止了 CEE 的治疗。总之，这项为期 12 个月的 CEE 试验并未增加大脑中 Cr 的浓度。我们的体外数据支持 CEE 在病理性和对照细胞中有一定的被动转运的观点，尽管应该使用更亲脂的分子或其他模拟 BBB 的细胞系统来更好地研究体内系统。
