NOVEL THERAPY: GI COMPLICATIONS IN SIV INFECTED MACAQUES

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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.