The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis.

Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis.

Biomarkers of Glycosaminoglycans (GAG) accumulation in patients with mucopolysaccharidosis type VI-LeukoGAG, Corneal Opacification (COM) and Carotid Intima Media Thickening (CIMT).

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal storage disorder characterized by deficient activity of arylsulfatase B enzyme (ASB) resulting in cellular accumulation of dermatan sulfate (DS) and chondroitin sulfate (CS) that leads to cell injury. Urinary glycosaminoglycans (GAG) are often used as a biomarker in MPS diseases for diagnosis and to monitor treatment efficacy. This study evaluated leukocyte GAGs (leukoGAG) and skin GAGs as alternate biomarkers representing intracellular GAG changes in patients with MPS VI and treated with enzyme replacement therapy (ERT).

Reduction of lysosome abundance and GAG accumulation after odiparcil treatment in MPS I and MPS VI models.

Deficiencies of lysosomal enzymes responsible for the degradation of glycosaminoglycans (GAG) cause pathologies commonly known as the mucopolysaccharidoses (MPS). Each type of MPS is caused by a deficiency in a specific GAG-degrading enzyme and is characterized by an accumulation of disease-specific GAG species. Previously, we have shown the potential of the beta-D-xyloside, odiparcil, as an oral GAG clearance therapy for Maroteaux-Lamy syndrome (MPS VI), an MPS characterized by an accumulation of chondroitin sulphate (CS) and dermatan sulphate (DS).

CD8+T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas.

Tumor-infiltrating CD8 + T cells progressively lose functionality and fail to reject tumors. The underlying mechanism and re-programing induced by checkpoint blockers are incompletely understood. We show here that genetic ablation or pharmacological inhibition of histone lysine methyltransferase Suv39h1 delays tumor growth and potentiates tumor rejection by anti-PD-1.