Open AccessChemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS
Author(s) -
Amaya Rando,
Miriam de la Torre,
Anna Martínez-Muriana,
Pilar Zaragoza,
Antonio Musarò,
Sara Hernández,
Xavier Navarro,
Janne M. Toivonen,
Rosario Osta
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0210752
Subject(s) - amyotrophic lateral sclerosis , antimetabolite , drug , medicine , sod1 , fluorouracil , motor neuron , pharmacology , mitoxantrone , drug repositioning , disease , cancer , chemotherapy
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.