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Updated: May 26, 2026
Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS)
Published on: March 17, 2012
Methylene blue administration fails to confer neuroprotection in two amyotrophic lateral sclerosis mouse models
J-N Audet1, G Soucy, J-P Julien
1Research Centre of CHUQ and Department of Psychiatry and Neurosciences, Laval University, 2705 Laurier Boulevard, QC, Canada G1V 4G2.
Abstract:
Approximately 20% cases of familial amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Recent studies have shown that methylene blue (MB) was efficient in conferring protection in several neurological disorders. MB was found to improve mitochondrial function, to reduce reactive oxygen species, to clear aggregates of toxic proteins, and to act as a nitric oxide synthase inhibitor. These pleiotropic effects of relevance to ALS pathogenesis led us to test MB in two models of ALS, SOD1(G93A) mice and TDP-43(G348C) transgenic mice. Intraperitoneal administration of MB at two different doses was initiated at the beginning of disease onset, at 90 days of age in SOD1(G93A) and at 6 months of age in TDP-43(G348C) mice. Despite its established neuroprotective properties, MB failed to confer protection in both mouse models of ALS. The lifespan of SOD1(G93A) mice was not affected by MB treatment. The declines in motor function, reflex score, and body weight of SOD1(G93A) mice remained unchanged. MB treatment had no effect on motor neuron loss and aggregation or misfolding of SOD1. A combination of MB with lithium also failed to provide benefits in SOD1(G93A) mice. In TDP-43(G348C) mice, MB failed to improve motor function. Cytosolic translocation of TDP-43, ubiquitination and inflammation remained also unchanged after MB treatment of TDP-43(G348C) mice.
Insights
Methylene blue (MB) showed neuroprotective promise but failed to improve outcomes in mouse models of amyotrophic lateral sclerosis (ALS). Studies in SOD1(G93A) and TDP-43(G348C) mice found no benefits in lifespan or motor function.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Familial amyotrophic lateral sclerosis (ALS) is often linked to SOD1 gene mutations.
- Methylene blue (MB) exhibits neuroprotective effects, including improved mitochondrial function and reduced oxidative stress, making it a potential therapeutic candidate for neurological disorders.
Purpose of the Study:
- To investigate the efficacy of methylene blue (MB) as a treatment for amyotrophic lateral sclerosis (ALS).
- To evaluate MB's effects in established mouse models of ALS, specifically SOD1(G93A) and TDP-43(G348C) transgenic mice.
Main Methods:
- Methylene blue (MB) was administered intraperitoneally to SOD1(G93A) and TDP-43(G348C) transgenic mice at disease onset.
- Treatment assessed effects on lifespan, motor function, reflex scores, body weight, motor neuron loss, protein aggregation, and TDP-43 pathology.
Main Results:
- MB treatment did not alter the lifespan or motor function decline in SOD1(G93A) mice.
- No significant changes were observed in motor neuron loss, SOD1 aggregation, or TDP-43 pathology in either mouse model.
- A combination of MB and lithium also failed to yield benefits in SOD1(G93A) mice.
Conclusions:
- Methylene blue (MB) does not confer protection in SOD1(G93A) or TDP-43(G348C) mouse models of amyotrophic lateral sclerosis (ALS).
- Despite its known neuroprotective properties, MB is ineffective for these specific ALS models, suggesting limitations in its therapeutic application for ALS.
