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

ABSTRACT: 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.

SUBMITTER: Rando A

PROVIDER: S-EPMC6331125 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Rando Amaya A de la Torre Miriam M Martinez-Muriana Anna A Zaragoza Pilar P Musaro Antonio A Hernández Sara S Navarro Xavier X Toivonen Janne M JM Osta Rosario R

PloS one 20190114 1

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 perfo ...[more]

PMID: 30640943

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