Early pridopidine treatment improves behavioral and transcriptional deficits in YAC128 Huntington disease mice

摘要: Pridopidine is currently under clinical development for Huntington disease (HD), with on-going studies to better characterize its therapeutic benefit and mode of action. was administered either prior the appearance phenotypes or in advanced stages YAC128 mouse model HD. In early treatment cohort, animals received 0, 10, 30 mg/kg pridopidine a period 10.5 months. late were treated 8 weeks 0 an escalating dose (10 over 3 weeks). Early improved motor coordination reduced anxiety- depressive-like mice, but it did not rescue striatal corpus callosum atrophy. Late treatment, conversely, only symptoms. RNA-seq analysis revealed that reversed transcriptional deficits, upregulating disease-specific genes are known be downregulated during HD, finding experimentally confirmed herein. This suggests exerts beneficial effects at level. Taken together, our findings support continued particularly disease, provide valuable insight into potential action pridopidine.