Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis
Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis
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DOI：
10.1016/j.jns.2005.04.011
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发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Abe, K
中科院分区：
文献类型：
--
作者：
Nagano, I;Ilieva, H;Abe, K
胰岛素样生长因子（IGF）-1已被证明在体外和体内对运动神经元具有保护作用，但在肌萎缩侧索硬化症（ALS）患者中皮下给药时疗效有限。为了检查IGF-1在家族性ALS小鼠模型中的可能有效性，通过将IGF-1连续递送到腰椎脊髓的鞘内空间中来治疗表达具有G93 A突变的人：Cu/Zn超氧化物歧化酶（SOD 1）的转基因小鼠。我们发现鞘内注射IGF-1改善了G93 A转基因小鼠的运动表现，延迟了临床疾病的发作，并延长了存活时间。此外，它增加了磷酸化Akt和ERK在脊髓运动神经元中的表达，并部分防止这些小鼠的运动神经元丢失。总之，结果表明，直接将IGF-1注入鞘内空间可能对ALS具有治疗益处。(C)2005 Elsevier B. V.保留所有权利。
Insulin-like growth factor (IGF)-1 has been shown to have a protective effect on motor neurons both in vitro, and in vivo, but has limited efficacy in patients with amyotrophic lateral sclerosis (ALS) when given subcutaneously. To examine the possible effectiveness of IGF-1 in a mouse model of familial ALS, transgenic mice expressing human: Cu/Zn superoxide dismutase (SOD1) with a G93A mutation were treated by continuous IGF-1 delivery into the intrathecal space of the lumbar spinal cord. We found that the intrathecal administration of IGF-1 improved motor performance, delayed the onset of clinical disease, and extended survival in the G93A transgenic mice. Furthermore, it increased the expression of phosphorylated Akt and ERK in spinal motor neurons, and partially prevented motor neuron loss in these mice. Taken together, the results suggest that direct administration of IGF-1 into the intrathecal space may have a therapeutic benefit for ALS. (C) 2005 Elsevier B.V. All rights reserved.