The nitrone compound OKN-007 delays motor neuron loss and disease progression in the G93A mouse model of Amyotrophic Lateral Sclerosis

Our study investigated the therapeutic potential of OKN-007 in the SOD1 G93A mouse model of amyotrophic lateral sclerosis (ALS). The impact of OKN-007, known for its antioxidant, anti-inflammatory, and neuroprotective properties, was tested at two doses (150 mg/kg and 300 mg/kg) at onset and late-stage disease. Results demonstrated a significant delay in disease progression at both doses, with treated mice showing a slower advance to severe disease stages compared to untreated controls. Transcriptomic analysis using bulk RNA sequencing identified dysregulated genes in G93A mice that were restored by OKN-007 treatment and pathways that showed altered expression in response to OKN-007. Overall, our findings suggest that OKN-007 holds potential as a disease-modifying treatment for ALS, although further research is needed to optimize dosing regimens and understand its long-term effects. Overall design: mRNA profiling of wildtype control mice and a transgenic model of ALS ( G93A mice), treated or not with drug OKN007 for a period of 90 days or 155 days (4 replicates for each setting)