Other Experimental Therapies

The development of cladarabine, a purine nucleoside analogue that preferentially targets resting and proliferating T and B lymphocytes while sparing neutrophils, monocytes, red blood cells, and platelets for the treatment of LE, was discontinued because of an unacceptable risk-benefit ratio. A similar compound, fludarabine, is currently undergoing a National Institutes of Health-sponsored trial (Strand 2000).

Bindarit is a propioic acid inhibitor that modulates cytokine and chemokine production in animal models of inflammation (Zoja et al. 1998). In an open-label pilot study using bindarit in 10 patients with lupus nephritis, a decrease in proteinuria was observed (Vigano et al. 1995). However, a follow-up placebo-controlled trial was never initiated.

Tamoxifen is an antiestrogen used for the treatment and prevention of breast cancer. In an SLE mice model (MRL-Ipr/Ipr), tamoxifen decreased proteinuria and increased murine survival (Wu et al. 2000). However, a double-blind crossover study in 11 patients with SLE did not reveal any significant clinical improvement, and most of the patients experienced severe side effects (Sturgess et al. 1984).

Many biologicals have been developed, and, according to preclinical data, some of them seemed to be promising candidates for the treatment of LE. Among several antibodies and fusion proteins that have been effective in first trials, many failed to be of significant clinical benefit and are not being further developed for LE therapy. This includes, for example, anti-CD154, the ligand for CD40 (Dumont 2002), anti-CD4, anti-CD5, ricin, an immunoconjugate, 3E10 monoclonal antibody vaccine, anti-CD40L hu5 c9, and human recombinant DNAse.

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