Comprehensive research on pathomechanism therapy of ALS and

在SOD1突变的转基因小鼠中，PI3K、Akt、bcl2等生存信号从症状前期开始下降。在这个转基因小鼠模型中，低氧后血管内皮生长因子的诱导大大减少。此外，谷氨酸能AMPA受体的减少也参与了ALS的发病机制。为了开发体内治疗ALS的方法，IGF-1被新开发用于实验小鼠和人类患者的鞘内注射。通过这种疗法，运动神经元被很好地保存下来，保留了生存信号。此外，鞘内注射IGF-1也保留了临床症状。对人类ALS患者进行9个月的治疗。因此，这一项目在今年有效地实现了，并取得了成功的成果。

With transgenic mice of mutant SOD1, survival signals such as PI3K, Akt, bcl2 were found to be decreased from early period of presymptomatic stage. VEGF induction after hypox is was greatly reduced in this transgenic mice model. Furthermore, reduction of glutamatergic AMPA receptor is also involved in the pathogenesis of the disease.For development of in vivo treatment for ALS, intrathecal injection of IGF-1 was newly developed for experimental mice and human patients. With this therapy, motor neurons were well preserved with retention of survival signals. Furthermore, intrathecal injection of IGF-1 also preserved clinical symptoms. of human ALS patients for 9 month of treatment. Thus this, project was effectively achieved this year with successful results.