LAGENBIO, Departamento de Anatomía, Embriología y Genética Animal, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
Instituto Agroalimentario de Aragón-IA2 (Universidad de Zaragoza-CITA), Zaragoza, Spain.
PLoS One. 2019 Jan 14;14(1):e0210752. doi: 10.1371/journal.pone.0210752. eCollection 2019.
Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease with no cure. Currently there are only two ALS drugs approved by the FDA, both with a limited therapeutic effect. In the search for drug candidates for ALS, we studied the effect of known stem cell mobilizing agents (treatment) and antimetabolite 5-fluorouracil (5-FU) (anti-treatment) in SOD1G93A model of ALS. Surprisingly, we found that anti-cancer drug 5-FU increases lifespan, delays the disease onset and improves motor performance in ALS mice. Although we were not able to demonstrate the mechanistic basis of the beneficial 5-FU action in ALS mice, our findings suggest that 5-FU or similar drugs are possible drug candidates for the treatment of motor neuron diseases through drug repurposing.
肌萎缩侧索硬化症（ALS）是一种致命的运动神经元疾病，目前尚无治愈方法。目前，FDA 仅批准了两种 ALS 药物，它们的治疗效果都很有限。在寻找 ALS 的药物候选物时，我们研究了已知的干细胞动员剂（治疗）和抗代谢物 5-氟尿嘧啶（5-FU）（抗治疗）在 ALS SOD1G93A 模型中的作用。令人惊讶的是，我们发现抗癌药物 5-FU 能延长寿命、延迟疾病发作并改善 ALS 小鼠的运动性能。尽管我们还不能证明 5-FU 在 ALS 小鼠中的有益作用的机制基础，但我们的研究结果表明，5-FU 或类似药物可能是通过药物再利用治疗运动神经元疾病的候选药物。
