Therapeutic effects of CuII(atsm) in the SOD1-G37R mouse model of amyotrophic lateral sclerosis.

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. [ABSTRACT FROM AUTHOR]