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

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 neurotransmission: dopamine levels increase in the early stages of the disease, while more advanced stages are characterised by reduced dopamine levels. Such a biphasic change potentially explains the alterations in motor symptoms: increased dopamine-production induces hyperkinetic movements early in the disease course, while depleted dopamine 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 present study aimed at exploring the effects of cariprazine, a dopamine D2-D3 partial agonist with high affinity to D3 receptors, on 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 method. In addition, improvement from BL to Week 8 and 12 was calculated for all motor items.

Results: Data of 16 patients were collected, but data of only 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 effectiveness of a D2-D3 partial agonist, cariprazine, in the treatment of HD. The findings of this study revealed that cariprazine was effective in the treatment of a wide range of motor symptoms associated with HD.

Keywords: Cariprazine; Huntington’s disease; Motor function; Reagila; Vraylar.