Wasting syndrome (cachexia) is a frequent complication of several chronic diseases, including AIDS, and cancer. Excessive production of cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), contribute to the development of cachexia. Several drugs target cytokines in the treatment of cachexia, but all suffer from undesirable and often dose-limiting side effects that can worsen a patients quality of life. In preliminary studies, Biosource Technologies, Inc. (BTI) discovered that its biosynthetic melanins down regulate the production/release of TNF-alpha, IL-1beta and IL-6, even in "activated" monocytes, and are orally bioavailable and safe at the levels required to achieve the desired effect. We also found that some of these melanins suppress the transmission of HIV-1 among infected human monocytes. BTI is planning development of its melanins as novel and safe anticachexics. To do so successfully and expeditiously, BTI proposes to select from its melanin library those compounds with preferred cytokine regulatory activity. Once those leads are selected, BTI will conduct the appropriate preclinical efficacy and safety studies that will support an IND application with the US FDA. PROPOSED COMMERCIAL APPLICATIONS: Biosynthetic melanins may provide effective therapy for cachexia caused by elevated cytokine production in patients with chronic infections, including AIDS, as well as cancer.