Ikeda Ken, Iwasaki Yasuo
Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan.
PLoS One. 2015 Oct 15;10(10):e0140316. doi: 10.1371/journal.pone.0140316. eCollection 2015.
Edaravone, a free radical scavenger is used widely in Japanese patients with acute cerebral infarction. This antioxidant could have therapeutic potentials for other neurological diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the upper and the lower motor neuron, leading to death within 3-5 years after onset. A phase III clinical trial of edaravone suggested no significant effects in ALS patients. However, recent 2nd double-blind trial has demonstrated therapeutic benefits of edaravone in definite patients diagnosed by revised El Escorial diagnostic criteria of ALS. Two previous studies showed that edaravone attenuated motor symptoms or motor neuron degeneration in mutant superoxide dismutase 1-transgenic mice or rats, animal models of familial ALS. Herein we examined whether this radical scavenger can retard progression of motor dysfunction and neuropathological changes in wobbler mice, sporadic ALS-like model. After diagnosis of the disease onset at the postnatal age of 3-4 weeks, wobbler mice received edaravone (1 or 10 mg/kg, n = 10/group) or vehicle (n = 10), daily for 4 weeks by intraperitoneal administration. Motor symptoms and neuropathological changes were compared among three groups. Higher dose (10 mg/kg) of edaravone treatment significantly attenuated muscle weakness and contracture in the forelimbs, and suppressed denervation atrophy in the biceps muscle and degeneration in the cervical motor neurons compared to vehicle. Previous and the present studies indicated neuroprotective effects of edaravone in three rodent ALS-like models. This drug seems to be worth performing the clinical trial in ALS patients in the United States of American and Europe, in addition to Japan.
依达拉奉是一种自由基清除剂，在日本急性脑梗死患者中广泛使用。这种抗氧化剂可能对其他神经系统疾病具有治疗潜力。肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，会影响上下运动神经元，发病后3至5年内导致死亡。一项依达拉奉的III期临床试验表明，其对ALS患者无显著疗效。然而，最近的第二项双盲试验证明，依达拉奉对根据修订的埃尔埃斯科里亚尔ALS诊断标准确诊的特定患者具有治疗益处。此前的两项研究表明，依达拉奉可减轻突变型超氧化物歧化酶1转基因小鼠或大鼠（家族性ALS的动物模型）的运动症状或运动神经元退化。在此，我们研究了这种自由基清除剂是否能延缓摇摆小鼠（散发性ALS样模型）运动功能障碍的进展和神经病理变化。在出生后3至4周诊断出疾病发作后，摇摆小鼠接受依达拉奉（1或10mg/kg，每组n = 10）或赋形剂（n = 10），通过腹腔注射每日给药4周。比较三组的运动症状和神经病理变化。与赋形剂相比，更高剂量（10mg/kg）的依达拉奉治疗显著减轻了前肢的肌肉无力和挛缩，并抑制了二头肌的失神经萎缩和颈运动神经元的退化。此前和目前的研究表明依达拉奉在三种啮齿动物ALS样模型中具有神经保护作用。除了日本，这种药物似乎值得在美国和欧洲的ALS患者中进行临床试验。
