Novel Therapeutic Target for the Treatment of Lupus
Annual rept. 1 Jul 2012-31 Jul 2013
LANKENAU INST OF MEDICAL RESEARCH WYNNEWOOD PA
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Many therapeutic strategies for SLE focus on the central role that autoantibody-producing B cells play in the pathology of this disorder. One general immunotherapeutic theme employs monoclonal antibodies mAb to interfere with, andor deplete, B cells to ultimately reduce disease causing autoantibody levels. However, current strategies are inherently limited because they are not specific for the disease state. Thus, treatments that can specifically block autoantibody production without compromising B cell function are needed. In our application we presented preliminary evidence in an in vivo model of a related autoimmune disease rheumatoid arthritis that showed antibodies to RhoB, a small GTPase blocked autoantibody secretion without affecting the overall B cell repertoire. This data led us to propose the purpose of this study, to evaluate the ability of anti-RhoB antibodies to reduce levels of pathologic autoantibodies, ultimately attenuating the severity of symptoms in the MRL-lpr murine model of SLE. We have not yet completed testing the anti-RhoB therapy in the SLE model, but plan to do so by the end of the award period. Presently our data suggests that dosing with the anti-RhoB antibodies produces a trend towards a decrease in autoantibody titers and proteinuria however, additional numbers are needed to achieve statistical significance. Over the remaining award period we will work to achieve statistical significance in our results.
- Anatomy and Physiology
- Medicine and Medical Research