DNA CHARCOAL PLASMA SORPTION FOR TREATMENT OF SLE

描述：（改编自申请人的摘要）长期 本提案的目的是开发一种基于体外吸附剂的 系统性红斑狼疮（SLE）和其他免疫系统疾病的治疗 紊乱 SLE的一个定义特征是血液中存在 抗DNA抗体（Ab），其水平与 疾病症状的严重程度。 目前的治疗方法效果甚微 或受到严重副作用的限制。 基于BioLogic-DT吸附剂的 血液透析系统已被证明可用于治疗肝衰竭 昏迷 通过将其与PF相结合， 辅助系统，允许直接处理等离子体， 粉末状吸附剂以去除大分子或蛋白质结合的分子。 使用DNA BioLogic-DTPF的PF单元中的免疫吸附剂将提供治疗 SLE急性加重的血液学表现， 降低抗DNA抗体水平。 DNA会与活性炭结合 其已经使用γ辐射用三氯乙烯基硅烷涂底漆，和 使用标准方法定量。 DNA活性炭的结合能力 来自纯化蛋白溶液或血清的单克隆抗DNA抗体将被 使用ELISA方法测定。DNA的流变特性- 炭悬浮液影响其在PF吸附剂泵送中的行为 系统也将进行评估。 拟定商业应用： 系统性红斑狼疮（SLE）是一种慢性、复发性免疫性疾病， 这种疾病的严重程度与抗DNA抗体水平有关。 狼疮基金会估计，大约140万美国人 患有SLE，75%的患者会经历严重的发作， 可以用DNA免疫吸附治疗。DNA免疫吸附具有 降低这些患者发病率和器官损伤的潜力， 减少或消除抗DNA抗体，并可能避免 需要有严重毒副作用的药物治疗。

DESCRIPTION: (Adapted from the applicant's abstract) The long-term objective of this proposal is to develop an extracorporeal sorbent based treatment for systemic lupus erythematosus (SLE) and other immunologic disorders. A defining feature of SLE is the presence in the blood of anti-DNA antibodies (Ab), the level of which is correlated with the severity of disease symptoms. Current treatments are marginally effective or limited by severe side effects. The BioLogic-DT sorbent-based hemodialysis system has proven useful in the treatment of liver failure with coma. This technology has been enhanced by combining it with a PF auxiliary system which permits the direct treatment of plasma with powdered sorbents to remove large or protein bound molecules. Use of DNA immunosorbent in the PF unit of the BioLogic-DTPF will provide a therapy for the hematologic manifestations of acute exacerbations of SLE while reducing the anti-DNA Ab level. DNA will be bound to activated charcoal which has been primed with trichlorovinylsilane using gamma radiation, and quantified using standard methods. The capacity of DNA-charcoal to bind monoclonal anti-DNA Ab from purified protein solution or serum will be determined using an ELISA method. The rheologic properties of the DNA- charcoal suspension affecting its behavior in the PF sorbent pumping system will also be evaluated. PROPOSED COMMERCIAL APPLICATION: Systemic lupus erythematosus (SLE) is a chronic, relapsing immune disorder, the severity of which is linked to anti-DNA antibody levels. The Lupus Foundation estimates that approximately 1.4 million Americans have SLE, and that 75% of patients will experience severe episodes which may be treatable with DNA immunoadsorption. DNA immunoadsorption has the potential to reduce morbidity and organ damage in these patients by reducing or eliminating the anti-DNA antibodies and possibly obviating the need for drug therapies with severe toxic side effects.