The improvement of motor symptoms in Huntington’s disease during cariprazine treatment

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Abstract Background: Huntington’s disease (HD) is a progressive neurodegenerative disease, characterised by motor disturbances and non-motor (i.e., psychiatric) symptoms. Motor symptoms are the hallmark features of HD and take many forms. Their emergence is related to alterations in striatal dopaminergic (DA) neurotransmission, with increased DA levels in the early, and reduced levels in the later stages of the disease. Such a biphasic change potentially explains the alterations in motor symptoms: increased DA-production induces hyperkinetic movements early in the disease course, while depleted DA storage leads to hypokinetic symptoms in the advanced phase. Dopamine D2-D3 partial agonists could be a promising treatment option in HD, as they have the potential to either elevate or lower the surrounding dopamine levels if the levels are too low or too high, respectively, potentially offering symptom-relief across the illness-course. Therefore, the efficacy of cariprazine, a dopamine D2-D3 partial agonist with high affinity to D3 receptors, was examined in influencing motor symptoms associated with HD.Methods: This was a single-centre, retrospective study where sixteen patients received off-label cariprazine treatment for 12 weeks (1.5-3 mg/day). Motor symptoms were evaluated using the Motor Assessment of the Unified Huntington’s Disease Rating Scale. Least Square (LS) Mean Changes from baseline (BL) to Week 8 and Week 12 in the Total Motor Score (TMS) were analysed using the Mixed Model for Repeated Measures. In addition, improvement from BL to Week 8 and 12 was calculated for all motor items.Results: Data of 15 patients were analysed as one patient dropped out due to non-compliance. Significant changes were observed from BL to Week 8 (LS Mean Change: -9.4, p < 0.0001) and to Week 12 (LS Mean Change: -12.8, p < 0.0001) in the TMS. The improvement was captured in the majority of motor functions, excluding bradykinesia and gait. Mild akathisia was the most commonly reported side-effect, affecting 3 patients.Conclusion: This is the first study investigating the effect of a D2-D3 partial agonist, cariprazine, in the treatment of HD. The findings of this study reveal that cariprazine was effective in the treatment of a wide range of motor symptoms associated with HD.

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