Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis
2008 | journal article
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Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis
Pitzer, C.; Krüger, C.; Plaas, C.; Kirsch, F.; Dittgen, T.; Müller, R. & Laage, R. et al. (2008)
Brain, 131(12) pp. 3335-3347. DOI: https://doi.org/10.1093/brain/awn243
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Details
- Authors
- Pitzer, Claudia; Krüger, Carola; Plaas, Christian; Kirsch, Friederike; Dittgen, Tanjew; Müller, Ralph; Laage, Rico; Kastner, Stefan; Suess, Stefanie; Spoelgen, Robert; Henriques, Alexandre; Ehrenreich, Hannelore ; Schäbitz, Wolf-Rüdiger; Bach, Alfred; Schneider, Armin
- Abstract
- Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive lossof motoneurons, motor weakness and death within 1^5 years after disease onset. Therapeutic options remainlimited despite a substantial number of approaches that have been tested clinically. In particular, various neuro-trophic factors have been investigated. Failure in these trials has been largely ascribed to problems of insufficientdosing or inability to cross the blood^brain barrier (BBB).We have recently uncovered the neurotrophic propertiesof the haematopoietic protein granulocyte-colony stimulating factor (G-CSF).The protein is clinically well toler-atedandcrossestheintact BBB.Thisstudyexaminedthepotentialrole of G-CSFinmotoneurondiseases.Weinves-tigated the expression of the G-CSF receptor in motoneurons and studied effects of G-CSF in a motoneuron cellline and in the SOD1(G93A) transgenic mouse model.The neurotrophic growth factor was applied both by contin-uous subcutaneous delivery and CNS-targeted transgenic overexpression.This study shows that given at the stageof the disease where muscle denervation is already evident,G-CSF leads to significant improvement in motor per-formance, delays the onset of severe motor impairment and prolongs overall survivalof SOD1(G93A)tg mice.TheG-CSF receptoris expressedby motoneurons and G-CSF protects culturedmotoneuronalcells from apoptosis.InALS mice, G-CSF increased survival of motoneurons and decreased muscular denervation atrophy. Weconclude that G-CSF is a novel neurotrophic factor for motoneurons that is an attractive and feasible drug candi-date for the treatment of ALS.
- Issue Date
- 2008
- Journal
- Brain
- Language
- English