1. Chemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS
- Author
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Xavier Navarro, Sara B. Hernández, Anna Martínez-Muriana, Amaya Rando, Miriam de la Torre, Janne M. Toivonen, P. Zaragoza, Rosario Osta, and Antonio Musarò
- Subjects
Male ,0301 basic medicine ,amyotrophic lateral sclerosis ,Physiology ,Gene Expression ,Pharmacology ,Motor Neuron Diseases ,Mice ,Leukocyte Count ,0302 clinical medicine ,Animal Cells ,Medicine and Health Sciences ,Medicine ,Amyotrophic lateral sclerosis ,Musculoskeletal System ,media_common ,Mammals ,Motor Neurons ,Multidisciplinary ,Pharmaceutics ,Stem Cells ,Muscles ,Eukaryota ,Neurodegenerative Diseases ,Animal Models ,ALS, 5-FU ,Body Fluids ,Drug repositioning ,Blood ,medicine.anatomical_structure ,Experimental Organism Systems ,Neurology ,Vertebrates ,Female ,Fluorouracil ,Cellular Types ,Anatomy ,Stem cell ,Research Article ,Drug ,Antimetabolites, Antineoplastic ,medicine.drug_class ,Science ,media_common.quotation_subject ,SOD1 ,Mouse Models ,Bone Marrow Cells ,Mice, Transgenic ,Motor Activity ,Research and Analysis Methods ,Rodents ,Antimetabolite ,03 medical and health sciences ,Model Organisms ,Drug Therapy ,Genetics ,Animals ,Humans ,5-FU ,Superoxide Dismutase ,business.industry ,Therapeutic effect ,Organisms ,Drug Repositioning ,Biology and Life Sciences ,Cell Biology ,Motor neuron ,Hematopoietic Stem Cells ,medicine.disease ,Disease Models, Animal ,030104 developmental biology ,Skeletal Muscles ,Amniotes ,Animal Studies ,ALS ,business ,030217 neurology & neurosurgery - 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. 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.