Therapeutic Evaluation of Polyamine Analogue Drug Candidates against Enterocytozoon bieneusi in a SCID Mouse Model

摘要: Enterocytozoon bieneusi is the most common cause of chronic diarrhea in individuals with human immunodeficiency virus infection or AIDS, and there no effective therapy. The inhibitory activities polyamine analogues (PG-11157, PG-11158, PG-11302) against E. were evaluated SCID mice preconditioned anti-gamma interferon monoclonal antibody intraperitoneally (i.p.). Mice challenged orally 10(4) spores, groups treated i.p. 14 days later for 7 days. drugs determined by enumerating spores feces three times a week an immunofluorescence assay. Immunohistochemistry staining confirmed within enterocytes. Oral administration PG-11157 (at 150 75 mg/kg body weight/day) PG-11302 250 mg/kg/day) had significant activity (96.2 to 99.6%) that was slightly better than fumagillin (1 mg/kg/day; 93.7%). injection only at 20 mg/kg/day. While treatments considerably reduced levels spore excretion, neither nor able completely eliminate bieneusi, as excretion reappeared after end treatment. Drug toxicity apparent during treatment, but it disappeared These results warrant further examination PG-11302.