Publications by authors named "E Peelen"
Background: IMU-856 is an orally available and systemically acting small molecule modulator of sirtuin 6 (SIRT6), a protein that serves as a transcriptional regulator of bowel epithelium regeneration. We aimed to evaluate the safety, clinical activity, pharmacodynamics, and pharmacokinetics of IMU-856 in healthy participants and in patients with coeliac disease.
Methods: This study reports the results from a completed first-in-human, three-part, double-blind, randomised, placebo-controlled, clinical trial of IMU-856 in healthy participants and patients with coeliac disease done in Australia and New Zealand.
Article Synopsis
- Multiple sclerosis (MS) is an autoimmune disease that damages myelin in the central nervous system, leading to injury of brain and spinal cord cells due to immune cell infiltration, particularly by pro-inflammatory Th17 cells.
- The study investigated how these Th17 cells interact with oligodendrocytes (the myelin-producing cells) through specific adhesion molecules, finding that the presence of certain molecules like ALCAM helps these cells adhere, which can lead to cell death.
- Results showed that in the presence of inflammatory cytokines or activated T cells, the expression of MCAM decreased, offering protective insights that targeting ALCAM could reduce harmful interactions between Th17 cells and oligodendrocytes, potentially leading to new therapeutic strategies for
Article Synopsis
- The study investigates how autoreactive white blood cells, specifically CD4+ T lymphocytes, cross the blood-brain barrier, contributing to multiple sclerosis (MS) pathology.
- Researchers identified a protein called MCAM on brain endothelial cells that helps facilitate this migration of immune cells during neuroinflammation.
- Targeting MCAM could offer a new therapeutic strategy for treating MS by preventing the recruitment of these harmful T lymphocytes from the blood.
The bile-acid sensing nuclear farnesoid X receptor (FXR) is an attractive target for the treatment of hepatic and metabolic diseases, but application of this chemotherapeutic concept remains limited due to adverse effects of FXR activation observed in clinical trials. To elucidate the mechanistic basis of FXR activation at the molecular level, we have systematically studied FXR co-regulator interactions and dimerization in response to seven chemically diverse FXR ligands. Different molecular effects on FXR activation mediated by different scaffolds were evident and aligned with characteristic structural changes within the ligand binding domain of FXR.
View Article and Find Full Text PDFIntroduction: Vidofludimus calcium has shown anti-inflammatory effects in clinical trials of autoimmune diseases and recently demonstrated antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a double-blind, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy of vidofludimus calcium in patients hospitalized for coronavirus disease 2019 (COVID-19) in Europe and the USA.
Methods: Patients aged 18 years or older who positive for COVID-19 were randomized (1:1) to receive placebo or 45 mg vidofludimus calcium for 14 days with both groups receiving standard-of-care treatment.