title: Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment.
  
  
  RESULTS
  Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12.
  
  
  CONCLUSIONS
  Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.
authors: INSERM, U1118, Mécanismes Centraux et Péripheriques de la Neurodégénérescence Strasbourg, France ; UMRS1118, Fédération de Médecine Translationnelle de Strasbourg Université de Strasbourg, France.
authors: Alexandre
authors: A
authors: Henriques
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Stefan
authors: S
authors: Kastner
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Eva
authors: E
authors: Chatzikonstantinou
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Claudia
authors: C
authors: Pitzer
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Christian
authors: C
authors: Plaas
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Friederike
authors: F
authors: Kirsch
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Oliver
authors: O
authors: Wafzig
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Carola
authors: C
authors: Krüger
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Robert
authors: R
authors: Spoelgen
authors: INSERM, U1118, Mécanismes Centraux et Péripheriques de la Neurodégénérescence Strasbourg, France ; UMRS1118, Fédération de Médecine Translationnelle de Strasbourg Université de Strasbourg, France.
authors: Jose-Luis
authors: JL
authors: Gonzalez De Aguilar
authors: Medical Research Center, Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
authors: Norbert
authors: N
authors: Gretz
authors: Sygnis Bioscience GmbH & Co KG Heidelberg, Germany.
authors: Armin
authors: A
authors: Schneider
keywords: ALS; G-CSF; gene expression; laser microdissection; motoneuron; mouse model; neurodegeneration
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