title: G-CSF prevents the progression of structural disintegration of white matter tracts in amyotrophic lateral sclerosis: a pilot trial.
abstract: BACKGROUND
  The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and -regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.
  
  
  METHODS
  Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 µg/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.
  
  
  RESULTS
  Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.
  
  
  CONCLUSIONS
  Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00298597.
authors.affiliation: Department of Neurology, University Hospital Muenster, Muenster, Germany. duningt@uni-muenster.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Duning
authors.forename: Hagen
authors.initials: H
authors.lastname: Schiffbauer
authors.forename: Tobias
authors.initials: T
authors.lastname: Warnecke
authors.forename: Siawoosh
authors.initials: S
authors.lastname: Mohammadi
authors.forename: Agnes
authors.initials: A
authors.lastname: Floel
authors.forename: Katja
authors.initials: K
authors.lastname: Kolpatzik
authors.forename: Harald
authors.initials: H
authors.lastname: Kugel
authors.forename: Armin
authors.initials: A
authors.lastname: Schneider
authors.forename: Stefan
authors.initials: S
authors.lastname: Knecht
authors.forename: Michael
authors.initials: M
authors.lastname: Deppe
authors.forename: Wolf Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D003710:Demography; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010865:Pilot Projects; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor