Research Article Details
| Article ID: | A20023 |
| PMID: | 26201461 |
| Source: | Drugs |
| Title: | Non-Alcoholic Steatohepatitis: Limited Available Treatment Options but Promising Drugs in Development and Recent Progress Towards a Regulatory Approval Pathway. |
| Abstract: | The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing world-wide in parallel to the increase of the obesity epidemic. Insulin resistance (IR) and the accumulation of triglyceride-derived toxic lipid metabolites play a key role in its pathogenesis. Multiple biomarkers are being evaluated for the non-invasive diagnosis of NASH. However, a percutaneous liver biopsy is still the gold standard method; the minimal diagnostic criteria include the presence of >5% macrovesicular steatosis, inflammation, and liver cell ballooning. Several pharmaceutical agents have been evaluated for the treatment of NASH; however, no single therapy has been approved so far. Due to the increasing prevalence and the health burden, there is a high need to develop therapeutic strategies for patients with NASH targeting both those with early-stage disease as well as those with advanced liver fibrosis. There are unique challenges in the design of studies for these target populations. Collaborative efforts of health authorities, medical disease experts, and the pharmaceutical industry are ongoing to align options for a registrational pathway. Several companies pursuing different mechanisms of action are nearing the end of phase II with their candidates. This manuscript reviews those compounds with a variety of mode of actions that have been evaluated and/or are currently being tested with the goal of achieving a NAFLD/NASH indication. |
| DOI: | 10.1007/s40265-015-0437-3 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |