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1.
J Clin Med ; 9(11)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207828

RESUMO

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington's Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression.

2.
Artigo em Inglês | MEDLINE | ID: mdl-28428907

RESUMO

BACKGROUND: Huntington disease is a fatal, autosomal dominant, neurodegenerative disorder manifest by the triad of a movement disorder, behavioral disturbances, and dementia. At present, no curative or disease modifying therapies exist for the condition and current treatments are symptomatic. Palliative care is an approach to care that focuses on symptom relief, patient and caregiver support, and end of life care. There is increasing evidence of the benefit of palliative care throughout the course of neurodegenerative conditions including Parkinson disease and amyotrophic lateral sclerosis. However, beyond its application at the end of life, little is known about the role of palliative care in Huntington disease. METHODS: In this article, we discuss what is known about palliative care in Huntington disease, specifically related to early disease burden, caregiver burnout, advance care planning, and end of life care. RESULTS: We provide a review of the current literature and discuss our own care practices. DISCUSSION: We conclude by discussing questions that remain unanswered and positing ideas for future work in the field.

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