NOVEL THERAPY: GI COMPLICATIONS IN SIV INFECTED MACAQUES

RDP58是SangStat医疗公司开发的一种新型肿瘤坏死因子抑制剂，口服给药后，已被证明成功地抑制了小鼠和猴子结肠炎模型的临床和组织学疾病。胃肠道并发症类似于慢性结肠炎，常见于艾滋病毒感染患者，导致营养吸收不良，营养不良，腹泻和体重减轻与快速的临床病程有关。肿瘤坏死因子在HIV感染者胃肠道炎症中的作用尚不清楚。在无症状患者的粘膜中检测到更高的水平，据报道，肿瘤坏死因子会增加艾滋病毒的复制。感染SIV的恒河猴是人类艾滋病的典型模型。本研究旨在分析RDP58疗法在治疗恒河猴SIV感染引起的肠道功能障碍和疾病中的抗炎应用。疗效分析将基于从疾病急性和无症状阶段的各种肠道功能参数获得的数据。将在不同的时间点对肠道活检样本进行细胞因子表达、上皮细胞损伤、细胞凋亡、细胞增殖、病毒载量和T细胞免疫表型特征的分析。这些动物将接受营养吸收效率的评估。在取得积极结果之前，RDP58将作为一种口服疗法用于患有艾滋病相关肠道并发症的患者进行测试。拟议的商业应用：在这些研究取得积极结果之前，RDP58在治疗艾滋病胃肠道并发症方面的治疗潜力具有至关重要的意义。

RDP58, a novel TNF inhibitor developed by SangStat Medical Corporation, has been shown to successfully suppress clinical and histological disease in mouse and monkey colitis models following oral administration. Gastrointestinal complications, similar to chronic colitis, are commonly seen in HIV-infected patients that lead to nutrient malabsorption, malnutrition, diarrhea and weight loss are related to a rapid clinical course. The role of TNF in gastrointestinal inflammation in HIV-infected individuals is unclear. Higher levels have been detected in the mucosa of asymptomatic patients and TNF has been reported to increase HIV replication. The SIV-infected rhesus macaque is a well- characterized model of human AIDS disease. The proposed study is designed to analyze the anti-inflammatory applications of RDP58 therapy in the treatment of intestinal dysfunction and disease caused by SIV infection in rhesus macaques. Analysis of efficacy will be based on data obtained from various parameters of intestinal function in acute and asymptomatic stages of disease. Intestinal biopsy samples will be analyzed at various time points for cytokine expression, epithelial cell damage, apoptosis, cell proliferation, viral loads and immunophenotypic characteristics of T cells. The animals will be evaluated for nutrient absorption efficiencies. Pending a positive outcome, RDP58 will be tested as an oral therapy in patients suffering from AIDS-related intestinal complications. PROPOSED COMMERCIAL APPLICATIONS: Pending a positive outcome of these studies, the therapeutic potential of RDP58 in treatment of gastrointestinal complications in AIDS is of paramount significance.