Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder. Generally, it is characterized by deficits in cognition, behavior, and movement. Recent studies have shown that pridopidine is a potential and effective drug candidate for the treatment of HD. In the present study, we performed a meta-analysis to evaluate the efficacy and safety of pridopidine in HD. Methods: The MEDLINE, EMBASE, CENTRAL, and Clinicaltrials.gov databases were searched for randomized controlled trials (RCTs) which had that evaluated pridopidine therapy in HD patients. Results: We pooled data from 1,119 patients across four RCTs. Patients in the pridopidine group had a significantly lower Unified Huntington's Disease Rating Scale (UHDRS)-modified Motor Score (mMS) (MD -0.79, 95% CI = -1.46 to -0.11, p = 0.02) than those in the placebo group. Additionally, no differences were observed in the UHDRS-Total Motor Score (TMS) (MD -0.91. 95% CI = -2.03 to 0.21, p = 0.11) or adverse events (RR 1.06, 95% CI = 0.96 to 1.16, p = 0.24) in the pridopidine and placebo groups. In the subgroup analysis, the short-term (<= 12 weeks) and long-term (>12 weeks) subgroups exhibited similar efficacy and safety with no statistical significance in TMS, mMS, or adverse events. However, TMS (MD -1.50, 95% CI = -2.87 to -0.12, p = 0.03) and mMS (MD -1.03, 95% CI = -1.87 to -0.19, p = 0.02) were observed to be improved significantly when the dosage of pridopidine >= 90 mg/day. Additionally, pridopidine (>= 90 mg/day) increased total adverse events (RR 1.11, 95%CI = 1.00 to 1.22, p = 0.04) compared with placebo. On this basis, we analyzed the incidence of various adverse events when the dosage was >= 90 mg/day. Nonetheless, these results were within the acceptable threshold, although patients developed symptoms, such as nasopharyngitis and insomnia. Conclusion: Pridopidine improved mMS and had no statistical significance in association with TMS or adverse events. Pridopidine (>= 90 mg/day) improved TMS and mMS but increased adverse events, such as nasopharyngitis and insomnia. More RCTs were expected to assess pridopidine in HD.

Automated summary

Pridopidine was found to improve motor scores in HD patients, with no significant adverse effects observed in both short-term and long-term use. However, when the dosage exceeded 90 mg/day, improvements in motor scores were seen but with increased risk of adverse events, such as nasopharyngitis and insomnia. Further randomized controlled trials are needed to evaluate the efficacy and safety of pridopidine in Huntington's disease.