How Zyprexa works
Huntington’s disease is caused by mutations in the huntingtin (HTT) gene. Long repeats of CAG nucleotides cause the huntingtin protein to be misfolded and degraded by the cell. This leads to the formation of toxic protein fragments that cause neurodegeneration, and result in chorea (tremors) and psychiatric symptoms.
Zyprexa’s mechanism of action is not well-understood. However, the compound is known to block or antagonize two types of key neural receptors: the D2 dopamine receptor and the 5HT2A serotonin receptor. These receptors bind to the neurotransmitters dopamine and serotonin, which serve many functions in neural signaling.
Blocking both the D2 and 5HT2A receptors is thought to decrease the overactive nerve signaling that causes tremors, as well as ease depression in Huntington’s patients.
Zyprexa in clinical trials
An small, open-label study, published in the journal Clinical Neuropharmacology in 2002, reported that 14 days of treatment with Zyprexa significantly reduced chorea in Huntington’s patients, as determined using the motor scale of the unified Huntington’s disease rating scale (UHDRS). Its researchers supported further studies into Zyprexa’s use, while noting that some patients required a “rather high dose” (30 mg daily) to benefit.
Another small-scale study, published in Acta Neurologica Scandinavica in 2002, evaluated Zyprexa given at a median daily 10 mg dose in nine Huntington’s patients treated for about one year. Assessments were carried out using the clinical global impression of change scale (CGIC) and the UHDRS (motor and behavioral scales) at six-month intervals. Psychiatric symptoms improved significantly under UHDRS-b scale, the researchers reported, and the treatment was “moderately effective for the motor symptoms.”
A Phase 3 clinical trial (NCT00632645) at a single site in France compared the relative benefits of three different oral treatments in 180 Huntington’s disease patients, randomly assigned to one year of treatment with either Zyprexa, tetrabenazine (brand name, Xenazine) or tiapride. The UHDRS-independence scale was the primary outcome measure assessed at 12 months, but motor, functional, psychiatric, and cognitive functions were also evaluated at three, six, nine and 12 months. The study is believe to have concluded in April 2017, but results have not yet been published.
Reported side effects of Zyprexa’s use include sedation, weight gain, dizziness, fatigue, and nausea.
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