Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials.

Background: Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist.

Methods: We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres.

Tasimelteon: a selective and unique receptor binding profile.

Hetlioz(®) (tasimelteon) is the first approved treatment in the United States for Non-24-Hour Sleep-Wake Disorder (Non-24). We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.

Absence of weight gain association with the HTR2C -759C/T polymorphism in patients with schizophrenia treated with iloperidone.

Weight gain is a common side effect of antipsychotics, contributing to poor treatment adherence, and previously linked to the -759C/T polymorphism near the serotonin receptor 2C gene. The effect of this polymorphism was analyzed in schizophrenia patients treated with iloperidone for up to 7 months. No association was detected with the modest weight changes observed in these patients.

Applicability of a genetic signature for enhanced iloperidone efficacy in the treatment of schizophrenia.

Objective: To demonstrate how several polymorphisms previously associated with the efficacy of the novel antipsychotic iloperidone could be used together to predict clinical response and provide practical information for individualized treatment.

Method: This inpatient randomized, double-blind, placebo- and ziprasidone-controlled, 28-day study of the efficacy of iloperidone was conducted from November 2005 to September 2006. Likelihood ratios, predicted probabilities of response, and number needed to treat were calculated for patients with schizophrenia (DSM-IV criteria) using 6 genetic markers of iloperidone response as measured by change in the Positive and Negative Syndrome Scale-Total (PANSS-T) score.

Common effect of antipsychotics on the biosynthesis and regulation of fatty acids and cholesterol supports a key role of lipid homeostasis in schizophrenia.

For decades, the dopamine hypothesis has gained the most attention in an attempt to explain the origin and the symptoms of schizophrenia. While this hypothesis offers an explanation for the relationship between psychotic symptoms and dopamine kinetics, it does not provide a direct explanation of the etiology of schizophrenia which remains poorly understood. Consequently, current antipsychotics that target neurotransmitter receptors, have limited and inconsistent efficacy.

Effect of a ciliary neurotrophic factor polymorphism on schizophrenia symptom improvement in an iloperidone clinical trial.

Aims: Presence of the null FS63TER allele of the rs1800169 polymorphism in the gene encoding the ciliary neurotrophic factor (CNTF) may increase the risk of schizophrenia. This study prospectively evaluated the CNTF rs1800169 genotype (G/G vs non-G/G) effects on response to iloperidone.

Patients & Methods: Iloperidone 24 mg/day was evaluated in a study of patients with schizophrenia.

A mutation in the human neurofilament M gene in Parkinson's disease that suggests a role for the cytoskeleton in neuronal degeneration.

Parkinson's disease (PD) is a common neurodegenerative movement disorder characterized by the destruction of dopaminergic neurons of the substantia nigra. We have identified a new mutation (Gly336Ser) in the medium neurofilament subunit in a patient of French-Canadian origin with early onset severe PD. This finding suggests, for the first time, that aberrations in neuronal molecules involved in the cytoskeleton could lead to the development of the pathology seen in PD.