TY  - JOUR
AU  - Hübener-Schmid, Jeannette
AU  - Kuhlbrodt, Kirsten
AU  - Peladan, Julien
AU  - Faber, Jennifer
AU  - Santana, Magda M
AU  - Hengel, Holger
AU  - Jacobi, Heike
AU  - Reetz, Kathrin
AU  - Garcia-Moreno, Hector
AU  - Raposo, Mafalda
AU  - van Gaalen, Judith
AU  - Infante, Jon
AU  - Steiner, Katharina M
AU  - de Vries, Jeroen
AU  - Verbeek, Marcel M
AU  - Giunti, Paola
AU  - Pereira de Almeida, Luis
AU  - Lima, Manuela
AU  - van de Warrenburg, Bart
AU  - Schöls, Ludger
AU  - Klockgether, Thomas
AU  - Synofzik, Matthis
AU  - Riess, Olaf
TI  - Polyglutamine-Expanded Ataxin-3: A Target Engagement Marker for Spinocerebellar Ataxia Type 3 in Peripheral Blood.
JO  - Movement disorders
VL  - 36
IS  - 11
SN  - 1531-8257
CY  - New York, NY
PB  - Wiley
M1  - DZNE-2021-01311
SP  - 2675 - 2681
PY  - 2021
AB  - 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.
KW  - Ataxin-3: genetics
KW  - Cross-Sectional Studies
KW  - Humans
KW  - Machado-Joseph Disease: drug therapy
KW  - Machado-Joseph Disease: genetics
KW  - Neurodegenerative Diseases
KW  - Peptides
KW  - ataxin-3; Machado-Joseph disease; spinocerebellar ataxia type 3; singulex technology; target engagement biomarker (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34397117
DO  - DOI:10.1002/mds.28749
UR  - https://pub.dzne.de/record/162615
ER  -