title: Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice.
abstract: This study investigated the effects of riluzole (Ril), creatine (Cr) and a combination of these treatments on the onset and progression of clinical signs and neuropathology in an animal model of familial amyotrophic lateral sclerosis, the G93A transgenic mouse (n=13-17 per group). The onset of clinical signs was delayed (P<0.05) by about 12 days in all treatment groups compared with control; however, no differences occurred between treatments. All animals were killed at 199 days of age. At the end of the experimental period the severity of clinical signs was less (P<0.05) with all treatments compared with control. Again no differences between treatments were observed. The treatments had no effect on the number of neurons in ventral horns of the lumbar region of the spinal cord. Transgenic mice ingesting Cr displayed elevated (P<0.05) total Cr levels in cerebral hemispheres (5%) and spinal cord (8%), but not skeletal muscles. These data demonstrate that treatment with Ril and Cr were both effective in delaying disease onset and clinical disability. To the age of killing, no additional benefit was conferred by co-administration of Ril and Cr.
authors.affiliation: School of Health Sciences, Deakin University, Victoria, 3125, Burwood, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Snow
authors.forename: J
authors.initials: J
authors.lastname: Turnbull
authors.forename: S
authors.initials: S
authors.lastname: da Silva
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: M A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D003401:Creatine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019782:Riluzole / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole; D013482:Superoxide Dismutase; D003401:Creatine