State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/199625 |
Resumo: | 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. |
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Furtado, Gabriel VasataOliveira, Camila Maria deBolzan, GabrielaSaute, Jonas Alex MoralesPereira, Maria Luiza SaraivaJardim, Laura Bannach2019-09-20T03:48:50Z20191415-4757http://hdl.handle.net/10183/199625001099984Machado-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.application/pdfengGenetics and molecular biology. Ribeirão Preto. Vol. 42, no. 1, suppl. (June 2019), p. 238-251Doença de Machado-JosephBiomarcadoresBiomarkersNeurophysiologyMachado-Joseph diseaseSpinocerebellar ataxia type 3State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to changeinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/otherinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001099984.pdf.txt001099984.pdf.txtExtracted Texttext/plain59668http://www.lume.ufrgs.br/bitstream/10183/199625/2/001099984.pdf.txtfa2686772ebc0502aa2bdddd700ce8cdMD52ORIGINAL001099984.pdfTexto completo (inglês)application/pdf652771http://www.lume.ufrgs.br/bitstream/10183/199625/1/001099984.pdf0b55f7900f1e5d319b10effaa01ca8f8MD5110183/1996252023-11-15 04:27:23.639051oai:www.lume.ufrgs.br:10183/199625Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-11-15T06:27:23Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change |
title |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change |
spellingShingle |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change Furtado, Gabriel Vasata Doença de Machado-Joseph Biomarcadores Biomarkers Neurophysiology Machado-Joseph disease Spinocerebellar ataxia type 3 |
title_short |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change |
title_full |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change |
title_fullStr |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change |
title_full_unstemmed |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change |
title_sort |
State biomarkers for Machado Joseph disease : validation, feasibility and responsiveness to change |
author |
Furtado, Gabriel Vasata |
author_facet |
Furtado, Gabriel Vasata Oliveira, Camila Maria de Bolzan, Gabriela Saute, Jonas Alex Morales Pereira, Maria Luiza Saraiva Jardim, Laura Bannach |
author_role |
author |
author2 |
Oliveira, Camila Maria de Bolzan, Gabriela Saute, Jonas Alex Morales Pereira, Maria Luiza Saraiva Jardim, Laura Bannach |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Furtado, Gabriel Vasata Oliveira, Camila Maria de Bolzan, Gabriela Saute, Jonas Alex Morales Pereira, Maria Luiza Saraiva Jardim, Laura Bannach |
dc.subject.por.fl_str_mv |
Doença de Machado-Joseph Biomarcadores |
topic |
Doença de Machado-Joseph Biomarcadores Biomarkers Neurophysiology Machado-Joseph disease Spinocerebellar ataxia type 3 |
dc.subject.eng.fl_str_mv |
Biomarkers Neurophysiology Machado-Joseph disease Spinocerebellar ataxia type 3 |
description |
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. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-09-20T03:48:50Z |
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2019 |
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http://hdl.handle.net/10183/199625 |
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1415-4757 |
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001099984 |
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http://hdl.handle.net/10183/199625 |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Genetics and molecular biology. Ribeirão Preto. Vol. 42, no. 1, suppl. (June 2019), p. 238-251 |
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