Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

Plasma pTau181 Predicts Clinical Progression in a Phase 2 Randomized Controlled Trial of the 11β-HSD1 Inhibitor Xanamem® for Mild Alzheimer's Disease.

Background: Blood biomarkers are proposed as a diagnostic alternative to amyloid PET or cerebrospinal fluid (CSF) analyses for the diagnosis of Alzheimer's disease (AD). Relatively little is known of the natural history of patients identified by different blood biomarkers.

Objective: To identify patients with elevated plasma phosphorylated tau (pTau)181 from a prior Phase 2a trial, and explore the natural histories of their clinical progression, and potential efficacy of Xanamem, a selective inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these patients.

Advantages and limits of remote consultations for HIV pre-exposure prophylaxis health pathway: ePrEP qualitative study.

Objective: Because of a high rate of HIV diagnosis and restricted medical access in the Centre-Val de Loire region in France , remote consultations (RC) with a community-based approach has been implemented to promote access to healthcare. Our study aimed to determine whether RC could improve access to pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) as part of the healthcare pathway associated with PrEP.

Materials And Methods: A qualitative approach involving semi-structured interviews with 17 MSM and 3 physicians from specialized sexual health centres was performed, with a mean duration of interview over one hour.

A Phase 1B Trial in GBA1-Associated Parkinson's Disease of BIA-28-6156, a Glucocerebrosidase Activator.

Background: Loss-of-function mutations in the GBA1 gene are one of the most common genetic risk factors for onset of Parkinson's disease and subsequent progression (GBA-PD). GBA1 encodes the lysosomal enzyme glucocerebrosidase (GCase), a promising target for a possible first disease-modifying therapy. LTI-291 is an allosteric activator of GCase, which increases the activity of normal and mutant forms of GCase.

A Biomarker Study in Patients with GBA1-Parkinson's Disease and Healthy Controls.

Background: Molecules related to glucocerebrosidase (GCase) are potential biomarkers for development of compounds targeting GBA1-associated Parkinson's disease (GBA-PD).

Objectives: Assessing variability of various glycosphingolipids (GSLs) in plasma, peripheral blood mononuclear cells (PBMCs), and cerebrospinal fluid (CSF) across GBA-PD, idiopathic PD (iPD), and healthy volunteers (HVs).

Methods: Data from five studies were combined.