Publications by authors named "Philippe Wiesel"
Background: Primary biliary cholangitis (PBC) is a rare liver disease with significant unmet need for second-line/add-on treatments. Setanaxib, a NOX1/4 inhibitor, has shown anti-fibrotic effects in in vitro and animal studies. This phase 2, randomized, multicentre study investigated the efficacy and safety of setanaxib in patients with PBC.
View Article and Find Full Text PDFBackground: There is a real unmet need for primary biliary cholangitis (PBC) treatments that can improve quality of life impacting symptoms. In this post hoc analysis, we evaluated potential effects of the NADP oxidase 1/4 inhibitor, setanaxib, on patient-reported quality of life from a phase 2 trial in PBC.
Patients And Methods: The underpinning double-blind, randomized, placebo-controlled trial (NCT03226067) recruited 111 patients with PBC and inadequate response/intolerance to ursodeoxycholic acid.
Determining mechanisms of resistance to αPD-1/PD-L1 immune-checkpoint immunotherapy is key to developing new treatment strategies. Cancer-associated fibroblasts (CAF) have many tumor-promoting functions and promote immune evasion through multiple mechanisms, but as yet, no CAF-specific inhibitors are clinically available. Here we generated CAF-rich murine tumor models (TC1, MC38, and 4T1) to investigate how CAFs influence the immune microenvironment and affect response to different immunotherapy modalities [anticancer vaccination, TC1 (HPV E7 DNA vaccine), αPD-1, and MC38] and found that CAFs broadly suppressed response by specifically excluding CD8 T cells from tumors (not CD4 T cells or macrophages); CD8 T-cell exclusion was similarly present in CAF-rich human tumors.
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- Diabetes leads to diabetic peripheral neuropathy (DPN), causing changes in peripheral nerves, and this study focuses on the roles of liver X receptor (LXR) signaling and NADPH oxidase-4 (Nox4) in its development.
- Research using diabetic mouse models and human skin samples shows that reduced LXR and increased Nox4 are linked to nerve damage and myelin gene expression issues in both type 1 and type 2 diabetes.
- Activating LXR or inhibiting Nox4 improves nerve function and restores important myelin proteins, indicating that targeting this LXR/Nox4 pathway could be a new treatment strategy for DPN.
Objective: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).
Methods: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals.