Skip Navigation


Brain Advance Access originally published online on October 3, 2008
Brain 2008 131(12):3335-3347; doi:10.1093/brain/awn243
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
131/12/3335    most recent
awn243v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Pitzer, C.
Right arrow Articles by Schneider, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pitzer, C.
Right arrow Articles by Schneider, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis

Claudia Pitzer1, Carola Krüger1, Christian Plaas1, Friederike Kirsch1, Tanjew Dittgen1, Ralph Müller1, Rico Laage1, Stefan Kastner1, Stefanie Suess1, Robert Spoelgen1, Alexandre Henriques1, Hannelore Ehrenreich2, Wolf-Rüdiger Schäbitz3, Alfred Bach1 and Armin Schneider1

1Sygnis Bioscience, Heidelberg, 2Max-Planck Institute of Experimental Medicine, Göttingen and 3Department of Neurology, University of Münster, Münster, Germany

Correspondence to: Dr Armin Schneider, Sygnis Bioscience, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany E-mail: schneider{at}sygnis.de

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive loss of motoneurons, motor weakness and death within 1–5 years after disease onset. Therapeutic options remain limited despite a substantial number of approaches that have been tested clinically. In particular, various neurotrophic factors have been investigated. Failure in these trials has been largely ascribed to problems of insufficient dosing or inability to cross the blood–brain barrier (BBB). We have recently uncovered the neurotrophic properties of the haematopoietic protein granulocyte-colony stimulating factor (G-CSF). The protein is clinically well tolerated and crosses the intact BBB. This study examined the potential role of G-CSF in motoneuron diseases. We investigated the expression of the G-CSF receptor in motoneurons and studied effects of G-CSF in a motoneuron cell line and in the SOD1(G93A) transgenic mouse model. The neurotrophic growth factor was applied both by continuous subcutaneous delivery and CNS-targeted transgenic overexpression. This study shows that given at the stage of the disease where muscle denervation is already evident, G-CSF leads to significant improvement in motor performance, delays the onset of severe motor impairment and prolongs overall survival of SOD1(G93A)tg mice. The G-CSF receptor is expressed by motoneurons and G-CSF protects cultured motoneuronal cells from apoptosis. In ALS mice, G-CSF increased survival of motoneurons and decreased muscular denervation atrophy. We conclude that G-CSF is a novel neurotrophic factor for motoneurons that is an attractive and feasible drug candidate for the treatment of ALS.

Key Words: ALS; growth factor; drug candidate; functional outcome; motoneuron survival

Abbreviations: ALS, amyotrophic lateral sclerosis; BBB, blood–brain barrier; CHAT, choline acetyltransferase; G-CSF, granulocyte-colony stimulating factor; SOD1, superoxide dismutase 1

Received March 18, 2008. Revised July 17, 2008. Accepted September 8, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.