Remogliflozin Etabonate Effect on Primary Biliary Cholangitis

瑞莫格列净依碳酸对原发性胆汁性胆管炎的影响

• 批准号: 10323592
• 负责人: william O wilkison
• 金额: $ 22.64万
• 依托单位: AVOLYNT, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323592
• 关键词: Address; Allium cepa; Animal Model; Animals; Antioxidants; Autoimmune; Bicarbonates; Bile Acids; Bile fluid; Biliary; Biochemistry; Biological Assay; Biological Markers; Cell physiology; Characteristics; Cholangitis; Chronic; Cirrhosis; Clinical; Clinical Research; Data; Development; Disease; Duct (organ) structure; Exhibits; FDA approved; Female; Fibrosis; Functional disorder; Gene Expression; Glucose; Glucose Transporter; Goals; Hepatocyte; Histology; Human; In Vitro; Inflammation; Interferon Type II; Kupffer Cells; Liver; Liver diseases; Marketing; Mediating; Messenger RNA; Mind; Mus; Oral Examination; Outcome; Oxidative Stress; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Placebos; Play; Primary biliary cirrhosis; Prodrugs; Property; Proteins; Quality of life; Reactive Oxygen Species; Research; Role; Sampling; Serum; Skin; Sodium; Testing; Time; Ursodeoxycholic Acid; absorption; base; bile duct; cholangiocyte; cholestatic liver disease; clinical examination; design; effective therapy; glucose uptake; improved; in vivo; inhibitor/antagonist; liver injury; liver transplantation; mouse model; novel strategies; prevent; programs; residence; side effect; stellate cell

Project Summary Primary biliary cholangitis (PBC) is a serious, chronic cholestatic liver disease characterized by a progressive, autoimmune-based destruction of the bile duct, and the eventual onset of cirrhosis and its complications. There are limited FDA-approved drugs for the management of PBC, but in many cases liver transplantation is required and offers the only chance for a complete cure. Therefore, effective treatments are urgently needed to treat PBC and to delay time to liver transplantation and to improve the quality of life for PBC patients. With that goal in mind, a novel approach for treating PBC is described below. These developments are based on the observation that remogliflozin etabonate, an SGLT2 inhibitor with unique differentiating properties from other SGLT2 inhibitors, prevents the progression of PBC disease pathology in a murine model of liver damage. Based on our compelling preliminary data, this Phase I confirmation of proof-of-concept study will demonstrate that remogliflozin etabonate is a potential therapy for PBC. We will achieve these goals by the following Aims: 1) Evaluate the role of remogliflozin and other SGLT inhibitors in liver cells in vitro. SGLTs are expressed in biliary ducts and inhibition of SGLTs causes increased biliary flow; and 2) Confirm in vivo our earlier observation that remogliflozin etabonate can prevent or reverse PBC progression using a well-accepted murine model of PBC.

项目总结