Abstract
Interleukin-1 inhibitors were tested in large arthritis trials with less than impressive results, despite having convincing disease expression data and pre-clinical animal model supporting the potential pathogenic role of this cytokine in these settings. Despite disappointing beginnings, some IL-1 pathway blocking drugs are now beginning to find a place in the pharmacopoeia of rheumatologists. Drug developers utilised rapidly growing understanding of the molecular pathway and the genetic basis of key diseases to seek out conditions in which IL-1 pathway activation was much more likely to have a pivotal role in disease pathogenesis compared to the major arthritides. This review details the crucial advances in understanding of the IL-1 pathway activation which enabled this progress, particularly the advent of inflammasome biology. The drug development of IL-1 biologics in rheumatological diseases makes a fascinating case study illustrating major changes in drug development strategy encompassing closer synergies between translational biology, underlying molecular pathophysiology of disease, and novel clinical development pathways of biologic therapeutics.
Keywords: Interleukin, interleukin-1, inflammasome, rheumatology, cryopyrin, gout, arthritis, CAPS.
Current Pharmaceutical Design
Title:Finding a Place for Interleukin-1 Inhibitors in the Treatment of Rheumatologic Diseases
Volume: 21 Issue: 17
Author(s): Donna Finch and Matthew Sleeman
Affiliation:
Keywords: Interleukin, interleukin-1, inflammasome, rheumatology, cryopyrin, gout, arthritis, CAPS.
Abstract: Interleukin-1 inhibitors were tested in large arthritis trials with less than impressive results, despite having convincing disease expression data and pre-clinical animal model supporting the potential pathogenic role of this cytokine in these settings. Despite disappointing beginnings, some IL-1 pathway blocking drugs are now beginning to find a place in the pharmacopoeia of rheumatologists. Drug developers utilised rapidly growing understanding of the molecular pathway and the genetic basis of key diseases to seek out conditions in which IL-1 pathway activation was much more likely to have a pivotal role in disease pathogenesis compared to the major arthritides. This review details the crucial advances in understanding of the IL-1 pathway activation which enabled this progress, particularly the advent of inflammasome biology. The drug development of IL-1 biologics in rheumatological diseases makes a fascinating case study illustrating major changes in drug development strategy encompassing closer synergies between translational biology, underlying molecular pathophysiology of disease, and novel clinical development pathways of biologic therapeutics.
Export Options
About this article
Cite this article as:
Finch Donna and Sleeman Matthew, Finding a Place for Interleukin-1 Inhibitors in the Treatment of Rheumatologic Diseases, Current Pharmaceutical Design 2015; 21 (17) . https://dx.doi.org/10.2174/1381612821666150310144603
DOI https://dx.doi.org/10.2174/1381612821666150310144603 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A Comparison of Biological Activity of B Lymphocyte Stimulator (BLyS) Antagonist Peptibodies and the Elucidation of Possible BLyS Binding Sites
Protein & Peptide Letters Expression and Functions of Vasoactive Substances Regulated by Hypoxia-Inducible Factor-1 in Chronic Hypoxemia
Cardiovascular & Hematological Agents in Medicinal Chemistry COX Selectivity and Animal Models for Colon Cancer
Current Pharmaceutical Design Advances in Analyses of Profens in Biological and Environmental Samples by Liquid Chromatography
Current Pharmaceutical Analysis Neurotransmitter Effects in Human Immunodeficiency Virus (HIV) and Simian Immuno-Deficiency Virus (SIV) Infection
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Protein-based Strategies of Molecular Therapy in Allergy
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Lentiviral Delivery of Proteins for Genome Engineering
Current Gene Therapy Chemistry and Biology of Anti-Inflammatory Marine Natural Products. Phospholipase A2 Inhibitors
Current Organic Chemistry Anti-inflammatory Action of Green Tea
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Editorial [Innovative Therapeutic Approaches for the Treatment of Pediatric Autoimmune and Inflammatory Diseases Executive (Guest Editor: Giorgio Zauli)]
Current Pharmaceutical Design Necroptosis: Who Knew There were so Many Interesting Ways to Die?
CNS & Neurological Disorders - Drug Targets The Targeted-liposome Delivery System of Antitumor Drugs
Current Drug Metabolism Herbal Phytochemicals as Immunomodulators
Current Immunology Reviews (Discontinued) Current Management of Neonatal Soft-tissue Sarcomas and Benign Tumors with Local Aggressiveness
Current Pediatric Reviews MicroRNAs as Early Biomarkers in Obesity and Related Metabolic and Cardiovascular Diseases
Current Pharmaceutical Design Natural Proteinaceous Inhibitors of Serine Proteases
Current Pharmaceutical Design Recent Concise Viewpoints of Chronic Active Epstein-Barr Virus Infection
Current Pediatric Reviews Functional Genomics Approaches in Cancer Research
Current Genomics Molecular Imaging of Apoptosis In Vivo with Scintigraphic and Optical Biomarkers – A Status Report
Anti-Cancer Agents in Medicinal Chemistry Recent Advances of Radionuclide-Based Molecular Imaging of Atherosclerosis
Current Pharmaceutical Design