Metformin treatment in young children with fragile X syndrome
Metformin treatment in young children with fragile X syndrome
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DOI：
10.1002/mgg3.956
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发表时间：
2019-09-14
影响因子：
2
通讯作者：
Hagerman, Randi J.
中科院分区：
文献类型：
--
作者：
Biag, Hazel Maridith B.;Potter, Laura A.;Hagerman, Randi J.
背景二甲双胍是一种常用于治疗2型糖尿病、肥胖和糖耐量异常的药物。它对儿童和成人都有很强的安全性。利用果蝇模型和脆性X综合征（FXS）基因敲除小鼠模型的研究发现，二甲双胍可以挽救记忆、社交新奇缺陷和神经解剖学异常。这些研究提供了初步证据，表明二甲双胍可用作与FXS相关的认知和行为问题的靶向治疗。此前，一项接受二甲双胍治疗的FXS儿童和成人病例系列显示，易激惹、社会反应、语言和多动得到改善。方法在这里，我们介绍了9名2至7岁的FXS儿童，他们接受了二甲双胍的临床治疗，并监测了行为和代谢变化。结果父母报告和二甲双胍前后的发育测试。大多数患者的语言发育和行为（如嗜睡和刻板）得到改善。结论这些结果支持二甲双胍在7岁以下FXS儿童中进行对照试验的必要性，这些儿童的大脑处于关键发育窗口期，因此可能会从二甲双胍中获得更大程度的临床获益。
Background Metformin is a drug commonly used in individuals with type 2 diabetes, obesity, and impaired glucose tolerance. It has a strong safety profile in both children and adults. Studies utilizing the Drosophila model and knock out mouse model of fragile X syndrome (FXS) have found metformin to rescue memory, social novelty deficits, and neuroanatomical abnormalities. These studies provided preliminary evidence that metformin could be used as a targeted treatment for the cognitive and behavioral problems associated with FXS. Previously, a case series of children and adults with FXS treated with metformin demonstrated improvements in irritability, social responsiveness, language, and hyperactivity. Methods Here, we present nine children with FXS between 2 and 7 years of age who were treated clinically with metformin and monitored for behavioral and metabolic changes. Results Parent reports and developmental testing before and after metformin are presented. There were improvements in language development and behavior (such as lethargy and stereotypy) in most of the patients. Conclusion These results support the need for a controlled trial of metformin in children with FXS under 7 years old whose brains are in a critical developmental window and thus may experience a greater degree of clinical benefit from metformin.