title: Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis.
abstract: There is currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS). Because recent evidence suggests that secondary inflammation and caspase activation may contribute to neurodegeneration in ALS, we tested the effects of minocycline, a second-generation tetracycline with anti-inflammatory properties, in mice expressing a mutant superoxide dismutase (SOD1(G37R)) linked to human ALS. Administration of minocycline into the diet, beginning at late presymptomatic stage (7 or 9 months of age), delayed the onset of motor neuron degeneration, muscle strength decline, and it increased the longevity of SOD1(G37R) mice by approximately 5 weeks for approximately 70% of tested mice. Moreover, less activation of microglia was detected at early symptomatic stage (46 weeks) and at the end stage of disease in the spinal cord of SOD1(G37R) mice treated with minocycline. These results indicate that minocycline, which is clinically well tolerated, may represent a novel and effective drug for treatment of ALS.
authors.affiliation: Centre for Research in Neurosciences, McGill University, Research Institute of the McGill University Health Centre, Montréal, Québec, H3G 1A4, Canada.
authors.forename: Jasna
authors.initials: J
authors.lastname: Kriz
authors.forename: Minh Dang
authors.initials: MD
authors.lastname: Nguyen
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000096:biosynthesis; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D008911:Minocycline