Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
PLoS One. 2011;6(10):e23141. doi: 10.1371/journal.pone.0023141. Epub 2011 Oct 6.
Methylene blue (MB) is a drug with a long history and good safety profile, and with recently-described features desirable in a treatment for ALS.
METHODOLOGY/PRINCIPAL FINDINGS: We tested oral MB in inbred high-copy number SOD1 G93A mice, at 25 mg/kg/day beginning at 45 days of age. We measured disease onset, progression, and survival. There was no difference in disease onset between MB-treated mice and controls, although subgroup analysis showed a modest but statistically significant delay in disease onset in MB-treated female mice only (control 122 ± 10.2 versus MB 129 ± 10.0 days). MB-treated mice of both sexes spent more time in less severe stages of disease, and less time in later, more severe stages of disease. There was a non-significant trend to longer survival in MB-treated animals (control males reached endpoint at 161 ± 14.1 days, versus 166 ± 10.0 days for MB-treated animals, and control females reached endpoint at 171 ± 6.2 days versus 173 ± 13.4 days for MB-treated animals).
CONCLUSIONS/SIGNIFICANCE: In spite of a strong theoretical rationale, MB had no significant effects on onset or survival in the inbred SOD1 G93A mouse model of ALS.
亚甲蓝（MB）是一种具有悠久历史和良好安全性的药物，最近描述的一些特性使其成为治疗 ALS 的理想选择。
方法/主要发现：我们在高拷贝数 SOD1 G93A 同系小鼠中测试了口服 MB，起始剂量为 25mg/kg/天，起始时间为 45 天。我们测量了疾病的发病、进展和存活率。MB 治疗组和对照组的疾病发病时间没有差异，但亚组分析显示，MB 治疗的雌性小鼠的发病时间有适度但具有统计学意义的延迟（对照组为 122 ± 10.2 天，MB 组为 129 ± 10.0 天）。MB 治疗的雌雄小鼠都在疾病较轻的阶段花费更多的时间，而在疾病较晚、较严重的阶段花费的时间更少。MB 治疗组的动物有更长的存活时间趋势，但无统计学意义（对照组雄性动物到达终点的时间为 161 ± 14.1 天，而 MB 治疗组为 166 ± 10.0 天，对照组雌性动物到达终点的时间为 171 ± 6.2 天，而 MB 治疗组为 173 ± 13.4 天）。
结论/意义：尽管有很强的理论依据，但 MB 对同系 SOD1 G93A 小鼠 ALS 模型的发病或存活没有显著影响。
