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Establishment of the amyotrophic lateral sclerosis therapy by midkine

中期因子治疗肌萎缩侧索硬化症的建立

基本信息

批准号：
17500229
负责人：
KATO Shinsuke
金额：
$ 2.14万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Since amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease with unknown etiology, the effective new therapy establishment is strongly desired. In this study, therefore, we have established the new ALS therapy by midkine (MK), which is one of nerve growth factors.For the establishment of the new ALS therapy by midkine, for the first time, we have produced two types of MK antibodies: one is a monoclonal antibody which recognizes only human MK and the other is a polyclonal antibody which recognizes MK among human, mouse, and rat. Second, we have analyzed 40 cases of human sporadic ALS and 5 cases of familial ALS with mutant SOD1 of two families, in addition to 3 lines of ALS animal models: G1 H-G93A mice, G93A rats, and H46R rats. In not only human autopsy cases but also ALS animal models, some motor neurons express MK in order to survive again ALS stress. Third we have produced MK overexpressing transgenic (MK-Tg) mice, which strongly express MK in motor neurons. Fourth, we have succeeded in producing mutation SOD1-MK overexpressing double transgenic (MK-ALS Tg) mice. MK-ALS Tg mice have shown a longer survival in comparison with ALS Tg mice clinically. In MK-ALS Tg mice, MK-histopathologically-overexpressing motor neurons have longer survived, compared with motor neurons without expression MK.This study results that MK protects motor neuron death caused by ALS, and provides a new ALS therapy by MK.

由于肌萎缩侧索硬化症（ALS）是一种病因不明的难治性神经退行性疾病，因此迫切需要建立有效的新疗法。 In this study, therefore, we have established the new ALS therapy by midkine (MK), which is one of nerve growth factors.For the establishment of the new ALS therapy by midkine, for the first time, we have produced two types of MK antibodies: one is a monoclonal antibody which recognizes only human MK and the other is a polyclonal antibody which recognizes MK among human, mouse, and rat.其次，我们分析了 40 例人类散发性 ALS 病例和 5 例具有两个家族 SOD1 突变的家族性 ALS，以及 3 个 ALS 动物模型：G1 H-G93A 小鼠、G93A 大鼠和 H46R 大鼠。不仅在人类尸检病例中，而且在 ALS 动物模型中，一些运动神经元表达 MK，以便再次在 ALS 应激下生存。第三，我们培育了 MK 过表达转基因 (MK-Tg) 小鼠，其在运动神经元中强烈表达 MK。第四，我们成功地产生了突变SOD1-MK过表达双转基因（MK-ALS Tg）小鼠。临床上，与 ALS Tg 小鼠相比，MK-ALS Tg 小鼠表现出更长的生存期。 In MK-ALS Tg mice, MK-histopathologically-overexpressing motor neurons have longer survived, compared with motor neurons without expression MK.This study results that MK protects motor neuron death caused by ALS, and provides a new ALS therapy by MK.