TitleTNP-470 is an effective antimicrosporidial agent.
Publication TypeJournal Article
Year of Publication1998
AuthorsCoyle, C, Kent, ML, Tanowitz, HB, Wittner, M, Weiss, LM
JournalJ Infect Dis
Date Published1998 Feb
KeywordsAnimals, Antibiotics, Antineoplastic, Cells, Cultured, Cyclohexanes, Encephalitozoon cuniculi, Encephalitozoonosis, Mice, Mice, Inbred BALB C, Mice, Nude, Microbial Sensitivity Tests, O-(Chloroacetylcarbamoyl)fumagillol, Sesquiterpenes

Therapy for microsporidia, which cause diarrhea and a wasting syndrome in persons with AIDS, has had limited success. Fumagillin, a naturally secreted water-insoluble antibiotic, has in vitro activity against microsporidia and has been used successfully in the treatment of superficial keratitis in patients with AIDS, but systemic therapy has been limited 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 infected 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 microg/mL. TNP-470 also demonstrated in vivo activity against Encephalitozoon cuniculi, with prolonged survival and the prevention of the development of ascites in infected athymic mice. These data suggest that the fumagillin derivative TNP-470 is a promising agent for the treatment of microsporidiosis.

Alternate JournalJ Infect Dis
PubMed ID9466552
Grant ListAI-31788 / AI / NIAID NIH HHS / United States