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

Rando, A. ; de la Torre, M. (Universidad de Zaragoza) ; Martinez-Muriana, A. ; Zaragoza, P. (Universidad de Zaragoza) ; Musaro, A. ; Hernández, S. ; Navarro, X. ; Toivonen, J.M. (Universidad de Zaragoza) ; Osta, R. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1371/journal.pone.0210752

Año: 2019

Publicado en: PLoS ONE 14, 1 (2019), e0210752 [16pp]
ISSN: 1932-6203

Factor impacto JCR: 2.74 (2019)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 27 / 71 = 0.38 (2019) - Q2 - T2

Factor impacto SCIMAGO: 1.023 - Multidisciplinary (Q1)

Financiación: info:eu-repo/grantAgreement/ES/FIS/PI14-00947
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI17-00949
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CB06-05-1105
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RD12-0019-0011
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RD16-0011-0035

Tipo y forma: Article (Published version)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)