The study on a new therapy of Menkes disease

门克斯病新疗法的研究

• 批准号: 10670759
• 负责人: KODAMA Hiroko
• 金额: $ 1.98万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670759/
• 关键词: Menkes disease; copper; chelating agent; threatment; macular mouse; macular マウス; 銅輸送ATPase; 銅投与; シチオカーボ

Menkes disease is a neurodegenerative disorder characterized by a copper deficiency in various organs including the brain and liver. On the contrary, copper accumulated in the kidney and intestine. These abnormalities of copper distribution are caused by a reduced membrane-transport of copper. We examined effects of a combination therapy of a subcutaneous copper administration and an oral administration of a chelating agent (N,N-diethyl carbamirate) on copper metabolism in the macular mouse, an animal model of Menkes disease. 【Materials and Methods】 Four weeks old macular mice and control mice were used. Copper (20μg/time) and diethyl carbamirate (0.05 mg/g body weight/time) were given twice a week for 4 weeks. After that, the mice were sacrificed, and the brain, liver, kidney and intestine were obtained. Copper concentrations in those tissues were analyzed with an atomic absorption spectrophotometer. The activity of cytochrome C oxidase in those tissues was also examined. 【Results and Discussion】 The copper concentration were improved in the brain and liver of macular mice that were treated with a combination of copper and a chelating agent. The copper concentrations were not changed in the kidney and intestine of the treated macular mice. However, the activities of cytochrome C oxidase were decreased in the brain and kidney of macular mice that were treated with the combination therapy. These results suggest that copper distribution was improved with the combination therapy, however, the copper enzyme activities were not improved by the therapy.

门克斯病是一种神经退行性疾病，其特征是包括大脑和肝脏在内的多个器官中铜缺乏，相反，铜在肾脏和肠道中积累，这些铜分布异常是由铜的膜转运减少引起的。皮下注射铜和口服螯合剂（N,N-二乙基氨基甲酸酯）联合疗法对门克斯病动物模型黄斑小鼠铜代谢的影响 [材料和方法] 四。周龄黄斑小鼠和对照小鼠每周两次给予铜（20μg/次）和氨基甲酸二乙酯（0.05mg/g体重/次），然后处死小鼠，并取脑。使用原子吸收分光光度计分析了这些组织中的铜浓度，并检查了这些组织中的细胞色素 C 氧化酶的活性。讨论】用铜和螯合剂联合治疗的黄斑小鼠的大脑和肝脏中的铜浓度得到改善，但治疗后的黄斑小鼠的肾脏和肠道中的铜浓度没有变化。接受联合疗法治疗的黄斑小鼠的大脑和肾脏中的细胞色素C氧化酶减少。这些结果表明联合疗法改善了铜的分布，但是该疗法并未改善铜酶活性。

项目成果

Kodama H, Murata Y, Mochizuki D, Kobayashi M, Yanagawa Y.: "Copper Metabolism and Mutation Analysis in Patients with Menkes Disease and Occipital Horn Syndrome."2nd Copper Homeostasis and Its Disorders: Molecular and Cellular Aspects. Ravello, Italy. 17-2

Kodama H、Murata Y、Mochizuki D、Kobayashi M、Yanakawa Y.：“门克斯病和枕角综合征患者的铜代谢和突变分析。”第 2 期铜稳态及其紊乱：分子和细胞方面。

Kodama H. et al.: "Clinical manifestations and treatment of Menkes disease and its variants"Pediatr Internal. 41. 423-429 (1999)

Kodama H.等人：“门克斯病及其变种的临床表现和治疗”Pediatr Internal。

児玉浩子(分担): "遺伝子治療開発ハンドブック"日本遺伝子治療学会. 5 (1999)

Hiroko Kodama（撰稿人）：“基因治疗开发手册”日本基因治疗学会 5 (1999)。

H.KODAMA et.al: "Structure and function of ATP7A as studied by mutotion analysis" 生体機能における金属イオンの特異的作用の分子科学. 3. 48 (1998)

H.KODAMA 等人：“通过突变分析研究 ATP7A 的结构和功能”金属离子对生物功能的特定影响的分子科学 3. 48 (1998)。

Kodama H, Murata Y.: "Molecular genetics and pathophysiology of Menkes disease"Pediatr International. 41. 430-435 (1999)

Kodama H、Murata Y.：“门克斯病的分子遗传学和病理生理学”Pediatr International。