A randomized, double‐blind, placebo‐controlled trial of pridopidine in Huntington's disease

Abstract

We examined the effects of 3 dosages of pridopidine, a dopamine-stabilizing compound, on motor function and other features of Huntington's disease, with additional evaluation of its safety and tolerability. This was a randomized, double-blind, placebo-controlled trial in outpatient neurology clinics at 27 sites in the United States and Canada. Two hundred twenty-seven subjects enrolled from October 24, 2009, to May 10, 2010. The intervention was pridopidine, either 20 (n=56), 45 (n=55), or 90 (n=58) mg daily for 12 weeks or matching placebo (n=58). The primary outcome measure was the change from baseline to week 12 in the Modified Motor Score, a subset of the Unified Huntington's Disease Rating Scale Total Motor Score. Measures of safety and tolerability included adverse events and trial completion on the assigned dosage. After 12 weeks, the treatment effect (relative to placebo, where negative values indicate improvement) of pridopidine 90 mg/day on the Modified Motor Score was -1.2 points (95% confidence interval [CI], -2.5 to 0.1 points; P = .08). The effect on the Total Motor Score was -2.8 points (95% CI, -5.4 to -0.1 points; nominal P = .04). No significant effects were seen in secondary outcome measures with any of the active dosages. Pridopidine was generally well tolerated. Although the primary analysis did not demonstrate a statistically significant treatment effect, the overall results suggest that pridopidine may improve motor function in Huntington's disease. The 90 mg/day dosage appears worthy of further study. Pridopidine was well tolerated.

The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults

“…In an earlier study, adding methylphenidate to levodopa treatment increased peak hand tapping speed in patients with PD compared to levodopa alone (Camicioli et al, 2001). Pridopidine, a dopamine-stabilizing compound, improved motor performance in patients with Huntington’s disease (Investigators, 2013), who showed decreased white matter integrity of the caudate, putamen and primary motor cortex in progression with their motor symptoms (Bohanna et al, 2011). Together, these studies suggested that patients with clinical conditions that implicate catecholaminergic dysfunction show altered motor cortical connectivity and performance that can be ameliorated by methylphenidate.…”

The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease

“…HD management is limited to supportive care and symptomatic treatment (Bates et al, 2015). Pridopidine (ACR16) is emerging in clinical trials as a potential therapeutic to mitigate motor symptoms ( e.g ., total motor score improvement was observed when tested as a secondary endpoint in two independent clinical trials) in HD patients (de Yebenes et al, 2011; Esmaeilzadeh et al, 2011; Huntington Study Group, 2013; Lundin et al, 2010). Pridopidine was initially identified as a stabilizer of the dopamine system, normalizing hyper- and hypodopaminergic behaviors, with the proposed mode of action of a D 2 receptor (D2R) antagonist, a partial weak agonist, or both a positive allosteric modulator and an orthosteric antagonist (Dyhring et al, 2010; Nilsson et al, 2004; Rung et al, 2008).…”

The effect of mild and moderate renal impairment on the pharmacokinetics of pridopidine, a new drug for Huntington's disease

“…In clinical trials conducted in HD patients, pridopidine at a dose of 45 mg twice daily non‐significantly improved the modified motor score (mMS) and significantly improved the total motor score (TMS) of the Unified Huntington's Disease Rating Scale (UHDRS). In both studies, pridopidine was considered safe and well tolerated with a benign adverse event (AE) profile 4, 5, 6.…”