Abstract
In Huntington's disease (HD), the main clinical symptoms include depression, apathy, cognitive deficits, motor deficiencies and involuntary movements. Cognitive, mood and behavioral changes may precede motor symptoms by up to 15 years. The treatment of these diverse symptoms is challenging. Tetrabenazine and deutetrabenazine are the only medications specifically approved for Huntington's chorea, but they do not affect the non-motor symptoms. For these, antidepressants, antipsychotics, and benzodiazepines have demonstrated benefit in some cases and can be used off-label. These drugs, due to sedative side effects, may negatively influence cognition. Sixteen patients having HD received a 12-week off-label cariprazine (CAR) treatment (1.5–3 mg/day). Cognitive performance and behavioral changes were measured by the Addenbrooke Cognitive Examination (ACE) test, the Cognitive and Behavioral part of the Unified Huntington's Disease Rating Scale (UHDRS), and the Beck Depression Inventory (BDI). Mixed model for repeated measures was fitted to the data, with terms of visit, baseline (BL) and their interaction. Cariprazine treatment resulted in the following changes from BL to week 12, respectively: the mean score of BDI decreased from 17.7 ± 10.7 to 10.0 ± 10.7 (p <0.0097), while the Behavioral Assessment score of the UHDRS decreased from 54.9 ± 11.3 to 32.5 ± 15.4 (p < 0.0001); ACE score increased from 75.1 ± 11.0 to 89.0 ± 9.3 (p < 0.0001); Cognitive Verbal Fluency score from 6.2 ± 2.5 to 7.7 ± 2.7 (p < 0.0103); Symbol Digit Test from 9.2 ± 6.9 to 12.3 ± 8.9 (p < 0.0009). Mild akathisia was the most frequent side effect, presenting in 2 out of 16 patients (12.5%). We conclude that CAR had a positive effect on depressive mood, apathy and cognitive functions in patients with early stage of HD. Based on the neurobiological basis of these symptoms, CAR can improve the dopamine imbalance of the prefrontal cortex. This draws attention to the transdiagnostic approach which supports the further understanding of the similar symptomatology of different neuropsychiatric disorders and helps to identify new indications of pharmaceutical compounds.
Highlights
Huntington’s DiseaseHuntington’s disease (HD) is an autosomal dominantly inherited polyglutamate repeat expansion disease causing neurodegeneration in the brain
In the huntingtin (HTT) gene the expansion of an unstable polymorphic trinucleotide repeat (CAG) region located within the open reading frame at the 5′ end of the first exon is responsible for the disease
This study aimed to explore the effects of 12-week cariprazine treatment on the mood and cognitive symptoms associated with Huntington’s disease
Summary
Huntington’s DiseaseHuntington’s disease (HD) is an autosomal dominantly inherited polyglutamate repeat expansion disease causing neurodegeneration in the brain. In the huntingtin (HTT) gene the expansion of an unstable polymorphic trinucleotide repeat (CAG) region located within the open reading frame at the 5′ end of the first exon is responsible for the disease. In HD individuals the range of the expanded CAG repeats is between 36 and 250 [1]. The pathomechanism is related to the CAG repeat expansion in the HTT gene, which results in complex pathophysiological changes [3] affecting mitochondrial function, mitophagy and immune system as well [4]. The clinical picture is dominated by motor symptoms (chorea, at end stage akinetic-rigorous hypokinesis), and non-motor features, such as cognitive dysfunction (including executive dysfunction, planning difficulties, cognitive decline), depression, apathy, irritability and behavioral disinhibition (e.g., making inappropriate comments, impulsivity, hypersexuality). Non-motor symptoms can appear before the motor symptoms, and are very strong predictors of loss of independence and quality of life
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
