The Efficacy and Safety of Pridopidine on Treatment of Patients with Huntington's Disease: A Systematic Review and Meta‐Analysis

Abstract

Background Pridopidine is a novel drug that helps stabilize psychomotor function in patients with Huntington's disease (HD) by activating the cortical glutamate pathway. It promises to achieve the unmet needs of current therapies of HD without worsening other symptoms. Objective To review the literature discussing the efficacy of pridopidine in alleviating motor symptoms and its safety in patients with HD. Methods We searched Scopus, Web of Science, the Cochrane Library, Wiley, and PubMed for randomized controlled trials (RCTs) of pridopidine on HD. Data from eligible studies were extracted and pooled as mean differences for efficacy and risk ratios (RRs) for safety using RevMan software version 5.3. Results A total of 4 relevant RCTs with 1130 patients were selected (816 in the pridopidine group and 314 in the placebo group). The pooled effect size favored pridopidine over placebo insignificantly in the Unified Huntington's Disease Rating Scale Total Motor Score (mean difference [MD], −0.93; 95% confidence interval [CI], −2.01 to 0.14; P = 0.09), whereas the effect size of 3 studies significantly favored pridopidine over placebo in the Unified Huntington's Disease Rating Scale Modified Motor Score (MD, −0.81; 95% CI, −1.48 to −0.13; P = 0.02). Pridopidine generally was well tolerated. None of the adverse effects were considerably higher in the case of pridopidine compared with placebo in overall adverse events (RR, 1.03; 95% CI, 0.94–1.13; P = 0.49) and serious adverse events (RR, 1.62; 95% CI, 0.88–2.99; P = 0.12). Conclusion The effects of pridopidine on motor functions (especially voluntary movements) in patients with HD are encouraging and provide a good safety profile that motivates further clinical trials on patients to confirm its effectiveness and safety.

Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington’s Disease: Mechanisms and Potential Therapeutics

“…Nevertheless, the use of pridopidine in HD has advanced into HD-focused clinical trials. Of note, the PRIDE-HD phase II exploratory trial (NCT02006472) documented a delay in the reduction in total functional capacity in HD patients over one year of pridopidine treatment, but is not known if BDNF up-regulation was responsible for this outcome [ 243 , 244 ]. Pridopidine is currently in a multicenter phase III clinical trial for patients with early-stage HD; however, this trial will not evaluate BDNF expression nor non-neuropsychological outcomes as part of its aims (NCT04556656).…”