Quiz Ref ID Huntington disease is a hereditary, progressive, neurodegenerative disease characterized by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Huntington disease is caused by an exon 1 CAG (cytosine-adenine-guanine [amino acid sequence]) trinucleotide expansion in the huntingtin (HTT) gene (NC_000004.12; http://www.ncbi.nlm.nih.gov/nuccore/568815594).¹ A prominent Huntington disease symptom is chorea, an involuntary, sudden movement that can affect any muscle and flow randomly across body regions.² Chorea can interfere with daily functioning and increase the risk of injury.³

Huntington disease (HD) is a hereditary, progressive, neurodegenerative disorder characterized by chorea and other motor symptoms, cognitive dysfunction, and psychiatric symptoms. Up to 90% of patients with HD have chorea that can interfere with daily function and may cause injury.^1,2 Tetrabenazine was the first drug approved by the US Food and Drug Administration for chorea associated with HD.³ High peak plasma concentrations and large plasma fluctuations may contribute to the tolerability issues observed in some patients with tetrabenazine use.⁴ Deutetrabenazine, a novel molecule that contains 6 deuterium atoms in place of 6 hydrogen atoms in specific positions in the tetrabenazine molecule, was approved for treating chorea associated with HD in 2017.⁵ Clinical evaluation in the First-HD trial found that deutetrabenazine provides significant chorea and motor improvement while maintaining a favorable safety profile when compared with placebo.⁶ The efficacy and excellent safety profile were attributed to the unique pharmacokinetic profile of deutetrabenazine, which enables comparable systemic exposure at lower doses, lower peak concentrations, and reduced plasma fluctuations.⁵ The current open-label study evaluated the safety and explored the efficacy of an overnight conversion from tetrabenazine to deutetrabenazine therapy with subsequent optional dose adjustment in patients with HD receiving a stable tetrabenazine regimen for chorea.

Tetrabenazine (TBZ) selectively depletes central monoamines by reversibly binding to the type-2 vesicular monoamine transporter. A previous double blind study in Huntington disease (HD) demonstrated that TBZ effectively suppressed chorea, with a favorable short-term safety profile (Neurology 2006;66:366-372). The objective of this study was to assess the long-term safety and effectiveness of TBZ for chorea in HD.

Huntington disease (HD) is a dominantly inherited progressive neurological disease characterized by chorea, an involuntary brief movement that tends to flow between body regions. HD is typically diagnosed based on clinical findings in the setting of a family history and may be confirmed with genetic testing. Predictive testing is available to those at risk, but only experienced clinicians should perform the counseling and testing. Multiple areas of the brain degenerate mainly involving the neurotransmitters dopamine, glutamate, and γ-aminobutyric acid. Although pharmacotherapies theoretically target these neurotransmitters, few well-conducted trials for symptomatic or neuroprotective interventions yielded positive results. Tetrabenazine (TBZ) is a dopamine-depleting agent that may be one of the more effective agents for reducing chorea, although it has a risk of potentially serious adverse effects. Some newer antipsychotic agents, such as olanzapine and aripiprazole, may have adequate efficacy with a more favorable adverse-effect profile than older antipsychotic agents for treating chorea and psychosis. This review will address the epidemiology and diagnosis of HD as background for understanding potential pharmacological treatment options. Because TBZ is the only US Food and Drug Administration-approved medication in the United States for HD, the focus of this review will be on its pharmacology, efficacy, safety, and practical uses. There are no current treatments to change the course of HD, but education and symptomatic therapies can be effective tools for clinicians to use with patients and families affected by HD.

Research from JAMA Neurology — Science and Ethics of Sham Surgery — A Survey of Parkinson Disease Clinical Researchers