An Alzheimer Disease Challenge Model: 24-Hour Sleep Deprivation in Healthy Volunteers, Impact on Working Memory, and Reversal Effect of Pharmacological Intervention: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

Purpose/background: Alzheimer disease (AD) is a public health issue because of the low number of symptomatic drugs and the difficulty to diagnose it at the prodromal stage. The need to develop new treatments and to validate sensitive tests for early diagnosis could be met by developing a challenge model reproducing cognitive impairments of AD. Therefore, we implemented a 24-hour sleep deprivation (SD) design on healthy volunteers in a randomized, double-blind, placebo-controlled, crossover study on 36 healthy volunteers.

Orphan drug clinical development.

Clinical development for orphan drugs is extremely demanding but fascinating. There is no single aspect that is really specific to it but instead it gathers most of the hurdles: design, outcomes, recruitment, ethics, cost, probability and predictability for success. To overcome these difficulties, there has to be a great collaboration between academic centers, small and large pharma companies, patients' representatives as well as health authorities to provide support and innovative approaches.

Fat fraction distribution in lower limb muscles of patients with CMT1A: A quantitative MRI study.

Objective: To quantitatively describe the MRI fat infiltration pattern of muscle degeneration in Charcot-Marie-Tooth (CMT) type 1A (CMT1A) disease and to look for correlations with clinical variables.

Methods: MRI fat fraction was assessed in lower-limb musculature of patients with CMT1A and healthy controls. More particularly, 14 muscle compartments were selected at leg and thigh levels and for proximal, distal, and medial slices.

Motor unit number index correlates with disability in Charcot-Marie-Tooth disease.

Objective: The aim of this study was to assess the usefulness of motor unit number index (MUNIX) technique in Charcot-Marie-Tooth disease and test the correlation between MUNIX and clinical impairment.

Methods: MUNIX technique was performed in the abductor pollicis brevis (APB), the abductor digiti minimi (ADM) and the tibialis anterior (TA) muscles in the nondominant side. A MUNIX sum score was calculated by adding the MUNIX of these 3 muscles.

Brain Networks are Independently Modulated by Donepezil, Sleep, and Sleep Deprivation.

Resting-state connectivity has been widely studied in the healthy and pathological brain. Less well-characterized are the brain networks altered during pharmacological interventions and their possible interaction with vigilance. In the hopes of finding new biomarkers which can be used to identify cortical activity and cognitive processes linked to the effects of drugs to treat neurodegenerative diseases such as Alzheimer's disease, the analysis of networks altered by medication would be particularly interesting.

Translational Identification of Transcriptional Signatures of Major Depression and Antidepressant Response.

Major depressive disorder (MDD) is a highly prevalent mental illness whose therapy management remains uncertain, with more than 20% of patients who do not achieve response to antidepressants. Therefore, identification of reliable biomarkers to predict response to treatment will greatly improve MDD patient medical care. Due to the inaccessibility and lack of brain tissues from living MDD patients to study depression, researches using animal models have been useful in improving sensitivity and specificity of identifying biomarkers.

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays.

Cytokines produced by both immune and non-immune cells are likely to play roles in the development and/or progression of psychiatric disorders. Indeed, many investigators have compared the blood cytokine levels in psychiatric patients with those of healthy controls or monitored their levels in patients during disease progression to identify biomarkers. Nevertheless, very few studies have confirmed that such cytokines remain stable in healthy individuals through periods of weeks and months.

Neurobehavioral and Cognitive Changes Induced by Hypoxia in Healthy Volunteers.

The early assessment of new symptomatic drugs against Alzheimer's disease remains difficult because of the lack of a predictive end-point. The use of a battery including different parameters could improve this early development. In order to test the reverse effect of symptomatic drugs in healthy volunteers, scientists have developed new experimental paradigms to artificially induce transient cognitive impairments in healthy volunteers akin to those observed in Alzheimer's disease, i.

An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A.

Background: Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss and muscle wasting. We favour the idea that diseases can be more efficiently treated when targeting multiple disease-relevant pathways. In CMT1A patients, we therefore tested the potential of PXT3003, a low-dose combination of three already approved compounds (baclofen, naltrexone and sorbitol).

Clinical spectrum and gender differences in a large cohort of Charcot-Marie-Tooth type 1A patients.

Introduction: Heterogeneous clinical presentation and gender differences were reported in Charcot-Marie-Tooth disease type 1A (CMT1A).

Methods: This report examined demographic and clinical data collected during a randomised controlled trial, to describe the clinical spectrum of a large and well-defined cohort of CMT1A patients.

Results: Among the 189 symptomatic patients screened, three patients (1.

Amygdala activity correlates with attentional bias in PTSD.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising in the aftermath of a traumatic event. The most prevalent hypothesis is that of an increased amygdala activity to threat cues. The amygdala has also shown an implication in orienting attention toward threat.

Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randomised, double-blind, placebo-controlled trial.

Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy that affects roughly one in 5000 births. No specific therapy currently exists for this degenerative disorder, which is characterised by distal progressive muscle atrophy and sensory loss, although ascorbic acid has been shown to reduce demyelination and improve muscle function in a transgenic mouse model of CMT1A. We tested the safety and efficacy of ascorbic acid in adults with CMT1A.