TNP-470 is an effective antimicrosporidial agent

Christina Coyle, Michael Kent, Herbert B. Tanowitz, Murray Wittner, Louis M. Weiss

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)515-518
Number of pages4
JournalJournal of Infectious Diseases
Volume177
Issue number2
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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