期刊
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
卷 14, 期 7-8, 页码 586-590出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/21678421.2013.824000
关键词
Amyotrophic lateral sclerosis (ALS); diacetylbis(4-methylthiosemicarbazone)-copper(II) [Cu-II(atsm)]; riluzole; rotarod; therapeutic
资金
- Australian National Health and Medical Research Council (NHMRC) [1005651]
- University of Melbourne
- Motor Neurone Disease Research Institute of Australia
- Australian Research Council (ARC)
Our objective was to assess the copper II complex of diacetylbis(4-methylthiosemicarbazone) [Cu-II(atsm)] for its preclinical potential as a novel therapeutic for ALS. Experimental paradigms used were designed to assess Cu-II(atsm) efficacy relative to treatment with riluzole, as a function of dose administered, and when administered post symptom onset. Mice expressing human Cu/Zn superoxide dismutase harbouring the disease-causing G37R mutation (SOD1-G37R) were used and effects of Cu-II(atsm) determined by assessing mouse survival and locomotor function (rotarod assay). Cu-II(atsm) improved SOD1-G37R mouse survival and locomotor function in a dose-dependent manner. The highest dose tested improved survival by 26%. Riluzole had a modest effect on mouse survival (3.3%) but it did not improve locomotor function. Cotreatment with Cu-II(atsm) did not alter the protective activity of Cu-II(atsm) administered on its own. Commencing treatment with Cu-II(atsm) after the onset of symptoms was less effective than treatments that commenced before symptom onset but still significantly improved locomotor function and survival. Improved locomotor function and survival of SOD1-G37R mice supports the potential for Cu-II(atsm) as a novel treatment option for ALS.
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