Lack of Effect of Methylene Blue in the SOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis
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BACKGROUND: 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.
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