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.

Déclaration de conflit d'intérêts

We have read the journal's policy and the authors of this manuscript have the following competing interests: Patent (RO, AR, JMT, PZ, AM) titled “Composiciones para el tratamiento de las enfermedades de las motoneuronas” (Compositions for the treatment of motor neurone diseases). Priority number: P201431825 (ES), 11 December 2014. This does not alter our adherence to PLOS ONE policies on sharing data and materials.