TY - JOUR
T1 - Chemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS
AU - Rando, Amaya
AU - De La Torre, Miriam
AU - Martinez-Muriana, Anna
AU - Zaragoza, Pilar
AU - Musaro, Antonio
AU - Hernández, Sara
AU - Navarro, Xavier
AU - Toivonen, Janne M.
AU - Osta, Rosario
PY - 2019/1/1
Y1 - 2019/1/1
N2 - © 2019 Rando et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.
AB - © 2019 Rando et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.
U2 - https://doi.org/10.1371/journal.pone.0210752
DO - https://doi.org/10.1371/journal.pone.0210752
M3 - Article
C2 - 30640943
VL - 14
M1 - e0210752
ER -
