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

AbstractOur objective was to assess the copperII complex of diacetylbis(4-methylthiosemicarbazone) [CuII(atsm)] for its preclinical potential as a novel therapeutic for ALS. Experimental paradigms used were designed to assess CuII(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 CuII(atsm) determined by assessing mouse survival and locomotor function (rotarod assay). CuII(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 CuII(atsm) did not alter the protective activity of CuII(atsm) administered on its own. Commencing treatment with CuII(atsm) after the onset of symptoms was less effective than t...