Development of a novel therapeutic approach for ALS using anti-TNF antibody

将小鼠抗TNF α抗体腹膜内施用至广泛用于肌萎缩侧索硬化症的动物模型的SOD 1小鼠。我们从生理学和病理学上评估了治疗的有效性或对疾病进展的抑制。在生理学评价中，包括寿命、体重和运动功能，未获得显著结果。然而，病理检查显示部分改善反应，包括运动神经元存活数和反应性胶质增生。这些结果进一步支持神经炎症参与运动神经元死亡的突变SOD 1可能在终末期。评估下游级联反应，如NF κ、JNK-AP-1和半胱天冬酶3，对于使用抗TNF α抗体优化治疗是必要的。

Mouse anti-TNF alpha antibody was intraperitoneally administered to SOD1 mice, which are widely used for animal model for amyotrophic lateral sclerosis. We physiologically and pathologically evaluated the efficacy of the therapy or suppression of disease progression. No significant result was obtained in physiological evaluations, including life span, body weight and motor functions. However, pathological examination revealed partial ameliorative response, including the numbers of survival motor neurons and the reactive gliosis. These results further supported involvement of neuroinflammation in motor neuron death by mutant SOD1 probably at the end stage. Evaluation of the downstream cascades, such as NF kappa, JNK-AP-1 and caspase 3, is necessary to optimize the therapy using the anti-TNF alpha antibody.