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Title: Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease
Authors: Esteves, Sofia
Duarte-Silva, Sara
Naia, Luana 
Neves-Carvalho, Andreia
Teixeira-Castro, Andreia 
Rego, Ana Cristina 
Silva-Fernandes, Anabela
Maciel, Patrícia 
Issue Date: 2015
Publisher: Public Library of Science
Project: Ataxia UK Grant (Project: Pharmacologic therapy for Machado-Joseph disease: from a C.elegans drug screen to a mouse model validation 
Serial title, monograph or event: PLoS ONE
Volume: 10
Issue: 10
Abstract: Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0141610
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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