＜シンポジウム35―5＞運動ニューロン疾患の分子病態の解明と治療法開発への展望
肝細胞増殖因子によるALSに対する新規治療法の開発
青木 正志, 割田 仁, 鈴木 直輝, 加藤 昌昭, 糸山 泰人
東北大学大学院医学系研究科神経内科〔〒980―8574 仙台市青葉区星陵町1―1〕
東北大学病院ALS治療開発センター
Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder characterized by the death of upper and lower motor neurons. Approximately 20% of familial ALS cases are caused by mutations in the superoxide dismutase 1 (SOD1) gene. We have developed rats that express a human SOD1 transgene with two different ALS-associated mutations develop striking motor neuron degeneration and paralysis. The larger size of this rat model as compared with the ALS mice will facilitate studies involving manipulations of spinal fluid (implantation of intrathecal catheters for chronic therapeutic studies; CSF sampling) and spinal cord (e.g., direct administration of viral- and cell-mediated therapies). Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. To examine both its protective effect on motor neurons and its therapeutic potential, we administered human recombinant HGF (hrHGF) by continuous intrathecal delivery to the transgenic rats at the onset of paralysis for 4 weeks. Intrathecal administration of hrHGF attenuates motor neuron degeneration and prolonged the duration of the disease by 63%. Our results indicated the therapeutic efficacy of continuous intrathecal administration of hrHGF in ALS rats. These results should prompt further clinical trials in ALS using continuous intrathecal administration of hrHGF.
Full Text of this Article in Japanese PDF (379K)
(臨床神経, 51：1195−1198, 2011)
key words：筋萎縮性側索硬化症，肝細胞増殖因子，髄腔内投与，遺伝子変異，トランスジェニックラット
（受付日：2011年5月20日）
