TNP-470 IS AN EFFECTIVE ANTIMICROSPORIDIAL AGENT

Therapy for microsporidia, which cause diarrhea and a wasting syndrome in persons with AIDS, has had limited success, Fumagillin, a naturall y secreted water-insoluble antibiotic, has in vitro activity against m icrosporidia and has been used successfully in the treatment of superf icial keratitis in patients with AIDS, but systemic therapy has been l imited by toxicity of the currently available fumagillin salt. TNP-470 , a semisynthetic analogue of fumagillin, was studied in vitro and in the athymic nude mouse model of microsporidiosis. RK13 cells were infe cted with microsporidia of the family Encephalitozoonidae and treated at day 3 with TNP-470. This agent was highly effective, with an ID50 ( 50% inhibitory dose compared with control) of 0.001 mu g/mL. TNP-470 a lso demonstrated in vivo activity against Encephalitozoon cuniculi, wi th prolonged survival and the prevention of the development of ascites in infected athymic mice, These data suggest that the fumagillin deri vative TNP-470 is a promising agent for the treatment of microsporidio sis.