Subscribe to RSS
DOI: 10.1055/s-0028-1109609
© Georg Thieme Verlag KG Stuttgart · New York
Monitoring der Therapie von Multiple-Sklerose-Patienten basierend auf Transkriptomuntersuchungen
Therapy Monitoring in Patients with Multiple Sclerosis Based on Transcriptomic AnalysisPublication History
Publication Date:
14 August 2009 (online)

Zusammenfassung
Die Multipe Sklerose (MS) stellt nach heutigem Erkenntnisstand eine multifaktorielle immunmediierte Erkrankung dar, deren Verlauf als auch Therapieansprechen von einer Reihe von Genen beeinflusst wird. Ein Ziel der biomedizinischen MS-Forschung ist die Bestimmung und Evaluierung der Expression prädisponierender Gene, die den Krankheitsverlauf und das Therapieansprechen vorhersagen (prognostische Biomarker). Solche Informationen können direkten Einfluss auf Auswahl und Optimierung von Therapeutika und für die Entwicklung von Behandlungsstrategien haben. Das genomweite RNA-Profil eines Individuums repräsentiert eine wichtige Komponente bei der umfassenden Bestimmung von krankheitsrelevanten oder Therapieresponse-assoziierten Faktoren. Es dient hiermit einem großangelegten Screening. Die vorliegende Arbeit liefert einen Überblick über den Stand der genomweiten Screeningmethoden auf Transkriptomebene in humanen peripheren Immunzellen bei MS.
Abstract
Multiple sclerosis (MS) is a multifactorial immune mediated disease; its course and response to therapy is influenced by various genes. A goal of the biomedical MS research is the discovery of sets of predisposing genes of which differential expression predict the disease course and outcomes of drug therapy. Such knowledge would have direct consequences for selection, refinement or development of treatments. The genome-wide RNA profile of an individual represents one component of the comprehensive determination of disease- or drug response-related elements; it serves as a large-scale approach. This work reviews the state of the art in MS research applying genomewide screening methods at the transcriptome level in peripheral immune cells of humans.
Schlüsselwörter
Multiple Sklerose - Therapieantwort - Genexpressionsprofile - Mikrochip - Lymphozyten
Key words
multiple sclerosis - therapy response - gene expression profiling - microarray - lymphocytes
Literatur
- 1
Lassmann H, Bruck W, Lucchinetti C.
Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy.
Trends Mol Med.
2001;
7
115-121
MissingFormLabel
- 2
Goodin D S.
Disease-modifying therapy in multiple sclerosis: update and clinical implications.
Neurology.
2008;
71
S8-S13
MissingFormLabel
- 3
Rieckmann P, Toyka K V. Multiple Sclerosis Therapy Consensus Group .
Immunmodulatorische Stufentherapie der Multiplen Sklerose.
Nervenarzt.
2002;
73
556-563
MissingFormLabel
- 4
Hemmer B, Hartung H P.
Toward the development of rational therapies in multiple sclerosis: what is on the
horizon?.
Ann Neurol.
2007;
62
314-326
MissingFormLabel
- 5
Villoslada P, Steinman L, Baranzini S E.
Systems biology and its application to the understanding of neurological diseases.
Ann Neurol.
2009;
65
124-139
MissingFormLabel
- 6
Vastag B.
Gene chips inch toward the clinic.
JAMA.
2003;
289
155-159
MissingFormLabel
- 7
Windeler J.
Prognosis – what does the clinician associate with this notion?.
Stat Med.
2000;
19
425-430
MissingFormLabel
- 8
Comabella M, Martin R.
Genomics in multiple sclerosis – current state and future directions.
J Neuroimmunol.
2007;
187
1-8
MissingFormLabel
- 9
Goertsches R H, Hecker M, Zettl U K.
Monitoring of multiple sclerosis immunotherapy: from single candidates to biomarker
networks.
J Neurol.
2008;
225 (Suppl 6)
48-57
MissingFormLabel
- 10
Sturzebecher S, Wandinger K P, Rosenwald A. et al .
Expression profiling identifies responder and non-responder phenotypes to interferon-beta
in multiple sclerosis.
Brain.
2003;
126
1419-1429
MissingFormLabel
- 11
Wandinger K P, Lunemann J D, Wengert O. et al .
TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta
treatment in multiple sclerosis.
Lancet.
2003;
361
2036-2043
MissingFormLabel
- 12
Baranzini S E, Mousavi P, Rio J. et al .
Transcription-based prediction of response to IFNbeta using supervised computational
methods.
PLoS Biol.
2005;
3
e2
MissingFormLabel
- 13
Goertsches R, Serrano-Fernández P, Möller S. et al .
Multiple sclerosis therapy monitoring based on gene expression.
Curr Pharm Des.
2006;
12
3761-3779
MissingFormLabel
- 14
Hecker M, Goertsches R H, Engelmann R. et al .
Integrative Modelling of Transcriptional Regulation in Response to Antirheumatic Therapy.
BMC Bioinformatics.
2009;
(in Revision)
MissingFormLabel
- 15
Fernald G H, Knott S, Pachner A. et al .
Genome-wide network analysis reveals the global properties of IFN-beta immediate transcriptional
effects in humans.
J Immunol.
2007;
178
5076-5085
MissingFormLabel
- 16
Palacios R, Goni J, Martinez-Forero I. et al .
A network analysis of the human T-cell activation gene network identifies JAGGED1
as a therapeutic target for autoimmune diseases.
PLoS ONE.
2007;
2
e1222
MissingFormLabel
- 17
Weinstock-Guttman B, Bhasi K, Badgett D. et al .
Genomic effects of once-weekly, intramuscular interferon-█1a treatment after the first
dose and on chronic dosing: Relationships to 5-year clinical outcomes in multiple
sclerosis patients.
J Neuroimmunol.
2008;
205
113-125
MissingFormLabel
- 18
Goertsches R, Hecker M, Koczan D. et al .
Biological function analyses of long-term genome wide blood RNA expression profiles
yield novel molecular response candidates for interferon beta treatment in relapsing
remitting multiple sclerosis.
Pharmacogenomics.
2009;
(in Revision)
MissingFormLabel
Prof. Dr. med. Uwe K. Zettl
Klinik und Poliklinik für Neurologie, Universität Rostock
Gehlsheimer Str. 20
18147 Rostock
Email: uwe.zettl@med.uni-rostock.de