Burge D J, Eisenman J, Byrnes-Blake K, Smolak P, Lau K, Cohen S B, Kivitz A J, Levin R, Martin R W, Sherrer Y, Posada J A
1 Resolve Therapeutics, LLC, Seattle, WA, USA.
2 Metroplex Clinical Research Center, Dallas, TX, USA.
Lupus. 2017 Jul;26(8):825-834. doi: 10.1177/0961203316678675. Epub 2016 Nov 16.
Blood-borne RNA circulating in association with autoantibodies is a potent stimulator of interferon production and immune system activation. RSLV-132 is a novel fully human biologic Fc fusion protein that is comprised of human RNase fused to the Fc domain of human IgG1. The drug is designed to remain in circulation and digest extracellular RNA with the aim of preventing activation of the immune system via Toll-like receptors and the interferon pathway. The present study describes the first clinical study of nuclease therapy in 32 subjects with systemic lupus erythematosus. The drug was well tolerated with a very favorable safety profile. The approximately 19-day serum half-life potentially supports once monthly dosing. There were no subjects in the study that developed anti-RSLV-132 antibodies. Decreases in B-cell activating factor correlated with decreases in disease activity in a subset of patients.
与自身抗体相关循环的血源RNA是干扰素产生和免疫系统激活的有效刺激物。RSLV-132是一种新型的全人源生物Fc融合蛋白，由与人IgG1的Fc结构域融合的人核糖核酸酶组成。该药物旨在保持在循环中并消化细胞外RNA，以防止通过Toll样受体和干扰素途径激活免疫系统。本研究描述了对32名系统性红斑狼疮患者进行核酸酶治疗的首例临床研究。该药物耐受性良好，安全性非常好。约19天的血清半衰期可能支持每月给药一次。该研究中没有受试者产生抗RSLV-132抗体。在一部分患者中，B细胞活化因子的降低与疾病活动度的降低相关。
