title: Electrophysiologic biomarkers for assessing disease progression and the effect of riluzole in SOD1 G93A ALS mice.
abstract: OBJECTIVE
  To compare electrical impedance myography (EIM) 50 kHz phase to weight, motor score, paw grip endurance (PGE), CMAP amplitude, and MUNE for the identification of disease progression and the effect of riluzole in the SOD1 G93A mouse.
  
  
  METHODS
  Twenty-three animals received 8 mg/kg/day riluzole in the drinking water starting at 6 weeks of age; 22 animals served as controls. Weight, motor score, PGE, CMAP, MUNE, and EIM were performed weekly to evaluate disease progression.
  
  
  RESULTS
  No difference in clinical disease onset or survival was found between treated and untreated groups. In addition, all methods failed to identify any beneficial effect of riluzole. Thus, data from all animals were combined for additional analyses. Of the 4 parameters, EIM phase showed the earliest change from baseline and the most linear decline throughout the entire measurement period. In addition, EIM phase correlated with PGE, CMAP amplitude, and MUNE (Spearman r = 0.92, 0.90, and 0.72, respectively, p<0.01 for all). The rate of EIM phase decline also correlated with individual animal survival (Spearman r = -0.31, p<0.05).
  
  
  CONCLUSIONS
  At this dose, riluzole is ineffective in slowing progression of ALS. However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing.
authors.affiliation: Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Minhee
authors.initials: M
authors.lastname: Sung
authors.forename: Seward B
authors.initials: SB
authors.lastname: Rutkove
mesh_terms: D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D017097:Electric Impedance; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology*; D009213:Myography; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019782:Riluzole / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D019782:Riluzole; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1