Novel multimeric IL-1 receptor antagonist for the treatment of rheumatoid arthritis.

Abstract

Protein therapeutics targeting inflammatory mediators have shown great promise for the treatment of autoimmunities such as rheumatoid arthritis (RA). However, a significant challenge in this area has been their low in vivo stability and consequently their severely compromised therapeutic efficacy. One such therapeutic molecule IL-1 receptor antagonist (IL-1ra), used in the treatment of rheumatoid arthritis, has displayed only modest efficacy in human clinical trials owing to its short biological half-life. Herein, we report a novel approach to conglomerate individual protein entities into a drug depot by incorporation of an amyloidogenic motif Lys-Phe-Phe-Glu (KFFE) thereby dramatically improving their systemic persistence and in turn their therapeutic efficacy in a mice model of autoimmune arthritis.

• Authors: Shweta Pasi, Ravi Kant, Sarika Gupta, Avadhesha Surolia
• Journal: Biomaterials (Biomaterials) Vol. 42 Pg. 121-33 (Feb 2015) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 25542800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Interleukin 1 Receptor Antagonist Protein

Topics

• Animals
• Arthritis, Experimental (drug therapy, pathology, radiography)
• Arthritis, Rheumatoid (drug therapy, pathology, radiography)
• Cell Line
• Disease Progression
• Humans
• Interleukin 1 Receptor Antagonist Protein (therapeutic use)
• Mice
• Microscopy, Atomic Force
• Protein Multimerization