Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study)
Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study)
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DOI：
10.1080/17482960600881870
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发表时间：
2006-12-01
影响因子：
--
通讯作者：
Kimura, Akio
中科院分区：
文献类型：
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作者：
Yoshino, Hiide;Kimura, Akio
肌萎缩侧索硬化症（ALS）是一种罕见的疾病，涉及选择性和进行性变性和消失的运动神经元。氧化应激被认为有助于其发病机制。我们研究了依达拉奉（一种自由基清除剂，以前被批准用于治疗急性脑梗死）在ALS患者中的疗效和安全性。在开放试验设计中，20例ALS受试者接受30 mg（5例受试者）或60 mg（15例受试者）依达拉奉静脉滴注，每日一次。给药2周后为2周观察期。这个四周的周期重复了六次。主要终点是修订的ALS功能评定量表（ALSFRS-R）评分的变化，而次要终点是脑脊液（CSF）中的3-硝基酪氨酸（3 NT）水平。在60 mg组中评价疗效。在6个月治疗期间，ALSFRS-R评分的下降（2.3 +/- 3.6分）显著小于依达拉奉给药前6个月的下降（4.7 +/- 2.1分）;两者之间的差异为2.4 +/- 3.5分（Wilcoxon符号秩检验，p=0.039）。在几乎所有患者中，CSF 3 NT（氧化应激的标志物）在6个月治疗期结束时显著降低至几乎检测不到的水平。本研究的数据表明，依达拉奉是安全的，可通过减少ALS患者的氧化应激来延缓功能性运动障碍的进展。
Amyotrophic lateral sclerosis (ALS) is a rare disease involving selective and progressive degeneration and disappearance of motor neurons. Oxidative stress is believed to contribute to its pathogenesis. We have investigated the efficacy and safety of edaravone, a free radical scavenger previously approved for treatment of acute cerebral infarction, in ALS patients. Within an open trial design, 20 subjects with ALS received either 30 mg (5 subjects) or 60 mg (15 subjects) of edaravone via intravenous drip once per day. Two weeks of administration was followed by a two-week observation period. This four-week cycle was repeated six times. The primary endpoint was the change in the revised ALS functional rating scale (ALSFRS-R) score, while the secondary endpoint was 3-nitrotyrosine (3NT) level in cerebrospinal fluid (CSF). Efficacy was evaluated in the 60 mg group. During the six-month treatment period, the decline in the ALSFRS-R score (2.3 +/- 3.6 points) was significantly less than that in the six months prior to edaravone administration (4.7 +/- 2.1 points); the difference between the two was 2.4 +/- 3.5 points (Wilcoxon signed rank test, p=0.039). In almost all patients, CSF 3NT, a marker for oxidative stress, was markedly reduced to almost undetectable levels at the end of the six-month treatment period. Data from the present study suggest that edaravone is safe and may delay the progression of functional motor disturbances by reducing oxidative stress in ALS patients.