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@ARTICLE{HbenerSchmid:162615,
author = {Hübener-Schmid, Jeannette and Kuhlbrodt, Kirsten and
Peladan, Julien and Faber, Jennifer and Santana, Magda M and
Hengel, Holger and Jacobi, Heike and Reetz, Kathrin and
Garcia-Moreno, Hector and Raposo, Mafalda and van Gaalen,
Judith and Infante, Jon and Steiner, Katharina M and de
Vries, Jeroen and Verbeek, Marcel M and Giunti, Paola and
Pereira de Almeida, Luis and Lima, Manuela and van de
Warrenburg, Bart and Schöls, Ludger and Klockgether, Thomas
and Synofzik, Matthis and Riess, Olaf},
collaboration = {Initiative, European Spinocerebellar Ataxia
Type-3/Machado-Joseph Disease},
title = {{P}olyglutamine-{E}xpanded {A}taxin-3: {A} {T}arget
{E}ngagement {M}arker for {S}pinocerebellar {A}taxia {T}ype
3 in {P}eripheral {B}lood.},
journal = {Movement disorders},
volume = {36},
number = {11},
issn = {1531-8257},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2021-01311},
pages = {2675 - 2681},
year = {2021},
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.},
keywords = {Ataxin-3: genetics / Cross-Sectional Studies / Humans /
Machado-Joseph Disease: drug therapy / Machado-Joseph
Disease: genetics / Neurodegenerative Diseases / Peptides /
ataxin-3; Machado-Joseph disease; spinocerebellar ataxia
type 3; singulex technology; target engagement biomarker
(Other)},
cin = {AG Gasser / Patient Studies Bonn / AG Klockgether},
ddc = {610},
cid = {I:(DE-2719)1210000 / I:(DE-2719)1011101 /
I:(DE-2719)1011001},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
experiment = {EXP:(DE-2719)ESMI-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34397117},
doi = {10.1002/mds.28749},
url = {https://pub.dzne.de/record/162615},
}