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State biomarkers for Machado Joseph disease: Validation, feasibility and responsiveness to change

Authors :
Laura Bannach Jardim
Gabriel Vasata Furtado
Camila Maria de Oliveira
Maria Luiza Saraiva-Pereira
Jonas Alex Morales Saute
Gabriela Bolzan
Source :
Genetics and Molecular Biology, Iss 0, Repositório Institucional da UFRGS, Universidade Federal do Rio Grande do Sul (UFRGS), instacron:UFRGS, Genetics and Molecular Biology, Issue: ahead, Published: 10 JUN 2019, Genetics and Molecular Biology, Genetics and Molecular Biology v.42 n.1 suppl.1 2019, Sociedade Brasileira de Genética (SBG), instacron:SBG, Genetics and Molecular Biology, Volume: 42, Issue: 1 Supplement 1, Pages: 238-251, Published: 10 JUN 2019
Publication Year :
2019
Publisher :
FapUNIFESP (SciELO), 2019.

Abstract

Machado-Joseph disease (SCA3/MJD) is the most common spinocerebellar ataxia worldwide, and particularly so in Southern Brazil. Due to an expanded polyglutamine at ataxin-3, SCA3/MJD presents a relentless course with no current disease modifying treatment. Clinical scales used to measure SCA3/MJD progression present moderate effect sizes, a major drawback for their use as main outcomes in clinical trials, given the rarity and slow progression of the disease. This limitation might be overcome by finding good surrogate markers. We present here a review of studies on peripheral and neurophysiological markers in SCA3/MJD that can be candidates for state biomarkers. Data on markers already studied were summarized, giving emphasis on validation against clinical scale, and responsiveness to change. While some biological fluid compounds and neurophysiological parameters showed poor responsiveness, others seemed to be good candidates. Some potential candidates that are waiting for responsiveness studies were serum levels of neuron specific enolase, vestibulo-ocular reflex and video-oculography. Candidates evaluated by RNA and microRNA expression levels need further studies to improve their measurements. Data on peripheral levels of Beclin-1 and DNAJB1 are promising but still incipient. We conclude that several potential candidates should follow onto validating studies for surrogate state biomarkers of SCA3/MJD.

Details

ISSN :
16784685 and 14154757
Volume :
42
Database :
OpenAIRE
Journal :
Genetics and Molecular Biology
Accession number :
edsair.doi.dedup.....97d7138be5e177a54beef2899eed9db9
Full Text :
https://doi.org/10.1590/1678-4685-gmb-2018-0103