Journal Article

DZNE-2021-01311

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Polyglutamine-Expanded Ataxin-3: A Target Engagement Marker for Spinocerebellar Ataxia Type 3 in Peripheral Blood.

Hübener-Schmid, J. ; Kuhlbrodt, K. ; Peladan, J. ; Faber, J.DZNE* ; Santana, M. M. ; Hengel, H.DZNE* ; Jacobi, H. ; Reetz, K. ; Garcia-Moreno, H. ; Raposo, M. ; van Gaalen, J. ; Infante, J. ; Steiner, K. M. ; de Vries, J. ; Verbeek, M. M. ; Giunti, P. ; Pereira de Almeida, L. ; Lima, M. ; van de Warrenburg, B. ; Schöls, L.DZNE* ; Klockgether, T.DZNE* ; Synofzik, M.DZNE* ; Initiative, E. S. A. T. D. (Collaboration Author) ; Riess, O.

2021
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/mds.28749

Abstract: Spinocerebellar ataxia type 3 is a rare neurodegenerative disease caused by a CAG repeat expansion in the ataxin-3 gene. Although no curative therapy is yet available, preclinical gene-silencing approaches to reduce polyglutamine (polyQ) toxicity demonstrate promising results. In view of upcoming clinical trials, quantitative and easily accessible molecular markers are of critical importance as pharmacodynamic and particularly as target engagement markers.We aimed at developing an ultrasensitive immunoassay to measure specifically polyQ-expanded ataxin-3 in plasma and cerebrospinal fluid (CSF).Using the novel single molecule counting ataxin-3 immunoassay, we analyzed cross-sectional and longitudinal patient biomaterials.Statistical analyses revealed a correlation with clinical parameters and a stability of polyQ-expanded ataxin-3 during conversion from the pre-ataxic to the ataxic phases.The novel immunoassay is able to quantify polyQ-expanded ataxin-3 in plasma and CSF, whereas ataxin-3 levels in plasma correlate with disease severity. Longitudinal analyses demonstrated a high stability of polyQ-expanded ataxin-3 over a short period. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keyword(s): Ataxin-3: genetics (MeSH) ; Cross-Sectional Studies (MeSH) ; Humans (MeSH) ; Machado-Joseph Disease: drug therapy (MeSH) ; Machado-Joseph Disease: genetics (MeSH) ; Neurodegenerative Diseases (MeSH) ; Peptides (MeSH) ; ataxin-3; Machado-Joseph disease; spinocerebellar ataxia type 3; singulex technology; target engagement biomarker

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Patient Studies Bonn (Patient Studies Bonn)
3. Patient Studies (AG Klockgether)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Experiment(s):

1. European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative

Appears in the scientific report 2021

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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