Synergistic therapeutic effects of combination of minocycline with memantine in amyotrophic lateral sclerosis mouse model

Abstract

Objective To investigate whether combination of minocycline with memantine would result in increased therapeutic effects in animal model of amyotrophic lateral sclerosis (ALS).Methods ALS mice were divided randomly into normal saline control group,minocycline group,memantine group and minocycline/memantine group.Motor strength,coordination,onset and mortality of ALS mice were evaluated after minocycline and/or memantine treatment.The weight of gastrocnemius was quantitatively analyzed as well.Results ( 1 ) Disease onset was delayed to 117 and 114 days respectively in the minocycline- and memantine-treated groups as compared with 98 days in the control group (P ＜ 0.05).Survival was similarly delayed in the minocycline and memantine groups to 146 and 143 days respectively as compared with 129 days in the control group ( P ＜ 0.05 ).Disease onset and survival in minocycline-memantine combination group were delayed to 126 and 159 days.Survival was extended by 13％,11％ and 23％ in the minocycline,memantine and minocycline-memantine groups respectively as compared with the control group; (2) The weight of gastrocnemius in minocycline group and memantine group was increased to 133.7 mg and 130.1 mg respectively as compared with 83.5 mg in the control group (P ＜0.05).The weight of gastrocnemius in minocycline-memantine group was 186.3 mg,which was significantly greater than in the control group,minocycline group or menmatine group (P ＜ 0.05).Conclusion Combination of minocycline and memantine in ALS mice model results in synergistic therapeutic effects. Key words: Amyotrophic lateral sclerosis; Treatment; Minocycline; Memantine