＜シンポジウム（3）―1―4＞アカデミア発の創薬
ALSに対するHGF
割田 仁, 加藤 昌昭, 鈴木 直輝, 糸山 泰人, 青木 正志
東北大学大学院医学系研究科神経内科学〔〒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 a devastating neurodegenerative disease characterized by selective loss of motor neurons. Approximately 20% of familial ALS cases are linked to mutations in Cu/Zn superoxide dismutase (SOD1) gene. Previously, we developed a transgenic rat model of ALS overexpressing mutant SOD1 protein. The rat model facilitates preclinical ALS research employing various therapeutic approaches such as intrathecal administration, cell transplantation, and viral vector-mediated gene transduction to the affected central nervous system. Hepatocyte growth factor (HGF) is a pleiotropic growth factor and also a potent survival-promoting factor for motor neurons. To examine its therapeutic effect on ALS, we administered human recombinant HGF (hrHGF) to the transgenic ALS rats. In contrast with vehicle-treated rats, continuous intrathecal infusion of hrHGF attenuated spinal motor neuron degeneration and prolonged the duration of the disease, even with administration from the onset of symptoms. To translate the strategy to human treatment, we performed dose-finding and safety studies using nonhuman primate model of contusive cervical spinal cord injury. Introducing exogenous HGF protein also revealed a distinct therapeutic effect with functional recovery. Given the therapeutic potential of hrHGF on ALS, we started a novel phase I clinical trial for ALS patients in Tohoku University Hospital.
Full Text of this Article in Japanese PDF (475K)
(臨床神経, 52：1214−1217, 2012)
key words：筋萎縮性側索硬化症，肝細胞増殖因子，髄腔内投与，治験，トランスジェニックラット
（受付日：2012年5月25日）
