FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular and mouse models of huntington disease

Alba Di Pardo, Enrico Amico, Mariagrazia Favellato, Roberta Castrataro, Sergio Fucile, Ferdinando Squitieri, Vittorio Maglione

Research output: Contribution to journalArticle

Abstract

Huntington disease (HD) is a genetic neurodegenerative disorder for which there is currently no cure and noway to stop or even slow the brain changes it causes. In the present study, we aimed to investigate whether FTY720, the first approved oral therapy for multiple sclerosis, may be effective inHDmodels and eventually constitute an alternative therapeutic approach for the treatment of the disease. Here, we utilized preclinical target validation paradigms and examined the in vivo efficacy of chronic administration of FTY720 in R6/2 HD mouse model. Our findings indicate that FTY720 improved motor function, prolonged survival and reduced brain atrophy in R6/2 mice. The beneficial effect of FTY720 administration was associated with a significant strengthening of neuronal activity and connectivity and, with reduction of mutant huntingtin aggregates, and it was also paralleled by increased phosphorylation of mutant huntingtin at serine 13/16 residues that are predicted to attenuate protein toxicity.

Original languageEnglish
Pages (from-to)2251-2265
Number of pages15
JournalHuman Molecular Genetics
Volume23
Issue number9
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology
  • Medicine(all)

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