title: 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.affiliation: Molecular Science Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Pasi
authors.affiliation: Molecular Science Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kant
authors.affiliation: Molecular Science Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Molecular Science Laboratory, National Institute of Immunology, New Delhi, India; Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. Electronic address: surolia@mbu.iisc.ernet.in.
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D018450:Disease Progression; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D051379:Mice; D018625:Microscopy, Atomic Force; D055503:Protein Multimerization; D011859:Radiography
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein
keywords: Anakinra; IL-1 receptor antagonist; Multimeric; Rheumatoid arthritis