Chemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS

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. This work was funded by Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) from the European Union (Grants PI14/00947 and PI17/00949), Asociación Adelante de La Roda, Plataforma Afectados por la ELA, Asociación Juntos Venceremos ELA, AVPA Zaragoza (RO), TERCEL (RD12/0019/0011 and RD16/0011/0035) and CIBERNED (CB06/05/1105) funds from the Instituto de Salud Carlos III of Spain (XN), and Fondazione Roma and Agenzia Spaziale Italiana (AM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.