The handle http://hdl.handle.net/1887/62616 holds various files of this Leiden University dissertation.
Author: Toonen, L.J.A.
Title: Developing an antisense oligonucleotide treatment for Spinocerebellar Ataxia Type 3
Issue Date: 2018-05-31
Developing an antisense oligonucleotiDe treatment for
spinocerebellar ataxia type 3
Lodewijk J.A. Toonen
with the authors.
No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without prior permission of the author.
Printing of this thesis was financially supported by ADCA vereniging Nederland
Developing an antisense oligonucleotiDe treatment for
spinocerebellar ataxia type 3
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op 31 mei 2018
klokke 15.00 uur
door
Lodewijk Julius Anton Toonen geboren te ‘s-Hertogenbosch
in 1988
leDen promotiecommissie:
Prof. Dr. A.M. Aartsma-Rus Prof. Dr. Harm H. Kampinga1 Dr. B. van de Warrenburg2
1 Afdeling Celbiologie, Faculteit Medische Wetenschappen/Universitair Medisch Centrum Groningen
2 Afdeling Neurologie, Donders Institute for Brain, Cognition and Behaviour, Radboud Universitair Medisch Centrum
table of contents
chapter 1 General introduction 7
Adapted from: Molecular neurobiology 2014, 49(3), 1513-1531
chapter 2 Antisense oligonucleotides in therapy for neurodegenerative disorders 31 Advanced Drug Delivery Reviews 2015, 87, 90-103
chapter 3 Antisense oligonucleotide-mediated exon skipping as a strategy to reduce
proteolytic cleavage of ataxin-3 69
Scientific Reports 2016, 6, 35200
chapter 4 Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model 91 Under revision; Molecular Neurodegeneration, 2018
chapter 5 Antisense oligonucleotide-mediated removal of the polyglutamine repeat in
spinocerebellar ataxia type 3 mice 131
Molecular Therapy Nucleic Acids 2017, 8, 232-242
chapter 6 Intracerebroventricular administration of a 2-‘O-methyl phosphorothioate antisense oligonucleotide results in activation of the innate immune system in
mouse brain 157
Nucleic Acid Therapeutics, 2018
chapter 7 Discussion 183
appendix Nederlandse samenvatting 205
List of publications 208
Curriculum vitae 209
Dankwoord 210
