Neuroprotection by chronic administration of Fluoroethylnormemantine (FENM) in mouse models of Alzheimer's disease.

Background: Fluoroethylnormemantine (FENM), a new Memantine (MEM) derivative, prevented amyloid-β[25-35] peptide (Aβ)-induced neurotoxicity in mice, a pharmacological model of Alzheimer's disease (AD) with high predictive value for drug discovery. Here, as drug infusion is likely to better reflect drug bioavailability due to the interspecies pharmacokinetics variation, we analyzed the efficacy of FENM after chronic subcutaneous (SC) infusion, in comparison with IP injections in two AD mouse models, Aβ-injected mice and the transgenic APP/PSEN1 (APP/PS1) line.

Methods: In Aβ-treated mice, FENM was infused at 0.

Real life data of ONC201 (dordaviprone) in pediatric and adult H3K27-altered recurrent diffuse midline glioma: Results of an international academia-driven compassionate use program.

Introduction: H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy.

Development of a pediatric oral solution of ONC201 using nicotinamide to enhance solubility and stability.

Diffuse intrinsic pontine glioma (DIPG) poses a significant treatment challenge in pediatric patients due to its aggressive nature and difficulty in crossing the blood-brain barrier with effective therapies. ONC201 (dordaviprone) shows promises in inducing apoptosis in cancer cells but suffers from poor water solubility and stability issues. Moreover, conventional solubilizing agents acceptable in formulations intended for adult patients are not suitable for pediatric use.

Visual Integration of Genome-Wide Association Studies and Differential Expression Results with the Hidecan R Package.

Background/objectives: We present hidecan, an R package for generating visualisations that summarise the results of one or more genome-wide association studies (GWAS) and differential expression analyses, as well as manually curated candidate genes, e.g., extracted from the literature.

Preformulation evaluation of selumetinib for topical application: skin distribution and photodegradation analysis using MALDI imaging and LC-MS/MS.

Understanding drug behavior within the skin, especially for photosensitive compounds, is crucial for developing effective and safe topical therapies. This study employs Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) to investigate the skin permeation and photostability of selumetinib, a MEK inhibitor used in treating type 1 neurofibromatosis (NF1). The highest amounts of selumetinib in the skin sections were obtained when using the gel formulation, suggesting that it is to be preferred to cream formulations to achieve higher permeation of the drug.