Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder, characterised by motor, cognitive, and behavioural deficits. Pridopidine belongs to a new class of compounds known as dopaminergic stabilisers, and results from a small phase 2 study in patients with Huntington's disease suggested that this drug might improve voluntary motor function. We aimed to assess further the effects of pridopidine in patients with Huntington's disease. METHODS: We undertook a 6 month, randomised, double-blind, placebo-controlled trial to assess the efficacy of pridopidine in the treatment of motor deficits in patients with Huntington's disease. Our primary endpoint was change in the modified motor score (mMS; derived from the unified Huntington's disease rating scale) at 26 weeks. We recruited patients with Huntington's disease from 32 European centres; patients were aged 30 years or older and had an mMS of 10 points or greater at baseline. Patients were randomly assigned (1:1:1) to receive placebo, 45 mg per day pridopidine, or 90 mg per day pridopidine by use of centralised computer-generated codes. Patients and investigators were masked to treatment assignment. We also assessed the safety and tolerability profile of pridopidine. For our primary analysis, all patients were eligible for inclusion in our full analysis set, in which we used the last observation carried forward method for missing values. We used an analysis of covariance model and the Bonferroni method to adjust for multiple comparisons. We used a prespecified per-protocol population as our sensitivity analysis. The α level was 0·025 for our primary analysis and 0·05 overall. This trial is registered with ClinicalTrials.gov, number NCT00665223. FINDINGS: At 26 weeks, in our full analysis set the difference in mean mMS was -0·99 points (97·5% CI -2·08 to 0·10, p=0·042) in patients who received 90 mg per day pridopidine (n=145) versus those who received placebo (n=144), and -0·36 points (-1·44 to 0·72, p=0·456) in those who received 45 mg per day pridopidine (n=148) versus those who received placebo. At the 90 mg per day dose, in our per-protocol population (n=114), the reduction in the mMS was of -1·29 points (-2·47 to -0·12; p=0·014) compared with placebo (n=120). We did not identify any changes in non-motor endpoints at either dose. Pridopidine was well tolerated and had an adverse event profile similar to that of placebo. INTERPRETATION: This study did not provide evidence of efficacy as measured by the mMS, but a potential effect of pridopidine on the motor phenotype of Huntington's disease merits further investigation. Pridopidine up to 90 mg per day was well tolerated in patients with Huntington's disease. FUNDING: NeuroSearch A/S.

Amantadine in the akinetic-rigid variant of Huntington's disease.

OBJECTIVE: To report the effects of amantadine on an akinetic-rigid variant of Huntington's disease (HD). CASE SUMMARY: We describe a 36-year-old woman with HD who was treated with intravenous amantadine for 5 days. The woman was evaluated with the Unified Huntington's Disease Rating Scale before and after treatment. Parkinsonism, bradykinesia, and dystonia improved significantly. DISCUSSION: Amantadine is a noncompetitive N-methyl d-aspartate receptor antagonist. It is mainly used in the treatment of Parkinson's disease, as it increases dopamine levels in the brain. This effect is said to ameliorate akinesia. Although the effect of amantadine on choreatic dystonia in HD has been reported in several studies, to the best of our knowledge, this is the first report of the ameliorative effects of amantadine on the rigid form of HD. Our patient showed improvements of gait, parkinsonism, and dystonia. Fine-motor tasks and eye movement did not change significantly. CONCLUSIONS: We suggest that amantadine treatment might be of value to patients with the akinetic-rigid variant of HD.