title: CGP 3466B has no effect on disease course of (G93A) mSOD1 transgenic mice.
abstract: BACKGROUND
  There is an accumulating body of evidence that apoptosis is involved in the motor neuron death that occurs in ALS, and in the (G93A) mSOD1 transgenic mouse model (mSOD1 mice). CGP 3466B, a tricyclic propargylamine structurally related to (-)-deprenyl, was found to inhibit apoptosis in a wide variety of in vitro and in vivo models. We therefore studied the effect of CGP 3466B in mSOD1 mice.
  
  
  METHODS
  As the effect of CGP 3466B was previously reported to have a bell-shaped curve, we performed a dose-ranging study. High-copy G93A mSOD1 mice were treated subcutaneously from the age of 50 days until death with four concentrations of CGP 3466B (0.39 microg kg(-1), 3.9 microg kg(-1), 39 microg kg(-1), and 390 microg kg(-1)). Behavioural tests were performed daily to determine disease onset, disease progression and survival. At the age of 110 days, two mice per group were sacrificed for histopathological analysis of the lumbar ventral horn and for semiquantitative analysis of motor neuron number.
  
  
  RESULTS
  We observed no effect on disease onset, disease progression, or survival of the mice. We also did not observe a significant effect on the number of motor neurons due to CGP 3466B.
  
  
  CONCLUSIONS
  We conclude that in high-copy G93A mSOD1 mice, chronic subcutaneous treatment with CGP 3466B offers no clinical benefit.
authors.affiliation: Department of Neurology, Laboratory for Experimental Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands. g.j.groeneveld@neuro.azu.nl
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Groeneveld
authors.forename: Freek L
authors.initials: FL
authors.lastname: van Muiswinkel
authors.forename: Judith
authors.initials: J
authors.lastname: de Leeuw van Weenen
authors.forename: Hylke
authors.initials: H
authors.lastname: Blauw
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: John H J
authors.initials: JH
authors.lastname: Wokke
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Peter R
authors.initials: PR
authors.lastname: Bär
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology; D010082:Oxepins / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D010082:Oxepins; C111178:dibenzo(b,f)oxepin-10-ylmethyl-methyl-prop-2-ynyl-amine; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase