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

Abstract:

:Huntington disease (HD) is a genetic neurodegenerative disorder for which there is currently no cure and no way 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 in HD models 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.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Di Pardo A,Amico E,Favellato M,Castrataro R,Fucile S,Squitieri F,Maglione V

doi

10.1093/hmg/ddt615

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

2251-65

issue

9

eissn

0964-6906

issn

1460-2083

pii

ddt615

journal_volume

23

pub_type

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