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

本研究探究了OKN-007在SOD1 G93A小鼠肌萎缩侧索硬化（amyotrophic lateral sclerosis, ALS）模型中的治疗潜力。OKN-007因其抗氧化、抗炎及神经保护特性而被广泛认知，本研究在疾病发作期与晚期两个阶段，以150 mg/kg与300 mg/kg两种剂量对其作用效果进行了测试。实验结果显示，两种给药剂量下小鼠的疾病进程均出现显著延缓，经OKN-007处理的小鼠相较于未给药对照组，进展至重症疾病阶段的速度更为缓慢。采用批量RNA测序（bulk RNA sequencing）开展的转录组学分析，鉴定出了G93A小鼠体内的失调基因，这些基因的表达异常可通过OKN-007给药得到恢复，同时明确了响应OKN-007给药后表达发生改变的信号通路。综上，本研究结果表明OKN-007有望成为治疗ALS的疾病修饰性治疗药物，不过仍需开展进一步研究以优化给药方案，并明确其长期作用效果。实验整体设计：对野生型对照小鼠与ALS转基因模型小鼠（G93A小鼠）开展mRNA表达谱分析，两组小鼠均接受或不接受OKN-007给药，给药周期分别为90天与155天，每组设置4个生物学重复。