AbetiMus

Abetimus (LJP 394 free base) is an immunosuppressant consisting of four double-stranded DNA (dsDNA) oligonucleotides. Abetimus is capable of crosslinking anti-dsDNA antibodies on the surface of B cells, and decreases anti-dsDNA antibodies levels. Abetimus has the potential for research of systemic lupus erythematosus[1].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

Administration of Abetimus (LJP 394 free base) is thought to reduce circulating anti-dsDNA Abs by at least two mechanisms. First, Abetimus (LJP 394 free base) acutely depletes circulating anti-dsDNA antibodies, presumably by forming small, soluble complexes that do not appear to result in significant activation of the complement system. Second, Abetimus (LJP 394 free base) binds B cells without T-cell activation, resulting in their apoptosis and reduced anti-dsDNA antibody production. In fact, Abetimus (LJP 394 free base) appears to induce B-cell tolerance by crosslinking anti-dsDNA surface immunoglobulin receptors on B cells and triggering the signal transduction pathways that lead to B-cell anergy or apoptosis[1].

Abetimus (LJP 394 free base) proves effective in suppressing anti-dsDNA-mediated pathologies in male BXSB mice, a model for systemic lupus. Mice dosed with Abetimus (3-300 μg/mouse) i.v. twice weekly, starting around nine weeks of age, has significantly lower titers of anti-dsDNA, lower numbers of anti-dsDNA-secreting spleen cells and less adverse renal histopathology than control mice[2]. Abetimus has a pharmacokinetic half-life ranging from 40 min to 1 h in mice[1].

[1]. Marta Mosca, et al. LJP-394 (abetimus sodium) in the treatment of systemic lupus erythematosus. Expert Opin Pharmacother. 2007 Apr;8(6):873-9.  

[2]. S M Coutts, et al. Pharmacological intervention in antibody mediated disease. Lupus. 1996 Apr;5(2):158-9.