Novel therapeutics for SLE

A recent review provides an update on new approaches to treat systemic lupus erythematosus (SLE), together with advances in our understanding of its pathogenesis with the potential for therapeutic advances.Introducing their review Dr Margrit Wiesendanger (Columbia University Medical Centre) and colleagues identify the goal of SLE therapy to be "reduction in both autoimmunity and target organ damage, maintenance of immune competence, and a low cost of therapy in side effects, both short term and long term".The authors consider antigen-targeted therapies, which may attenuate the immune response by decreasing exposure to the eliciting antigen, such as the DNase I enzyme and early complement components. Also, approaches to eliminate autoreactive cells using abetimus sodium (LJP 394) and methods to target DNA-specific B cells are discussed.Dr Wiesendanger and colleagues then review other cellular components involved in the pathogenesis of SLE including B cells, dendritic cells, and T cells together with their roles as autoreactive immune triggers, and therapeutic strategies targeting each group.After considering the process of immune call activation and opportunities for therapeutic intervention the authors focus on therapies that interfere with immune cell migration and approaches to mitigate end-organ damage.In particular, the role of TNF-alpha inhibitors and autologus stem cell transplantation are discussed, "if the morbidity and mortality of allogeneic stem cell transplantation can be reduced, this approach offers a potential for cure as the reconstituting immune system will not be predisposed to autoreactivity," Wiesendanger et al write.The group concludes that the introduction of novel therapeutics over the last few years is partly due to a greater understanding of the disease process. "A challenge for the future will be an understanding of the heterogeneity of the patient population, such that we can predict individual patients' clinical responses to therapy and likelihood of an adverse response. Equally importantly, we will need to identify combinations of reagents that can function synergistically to reduce lupus activity and limit immunosuppression," they conclude.Reference:...