Therapies for
microsporidiosis in humans are limited, and
fumagillin, which appears to be the most broadly effective antimicrosporidial
drug, is considered to be moderately toxic. The purpose of this study was to apply an in vitro
drug screening assay for Encephalitozoon intestinalis and Vittaforma corneae and an in vivo athymic mouse model of V. corneae
infection to assess the efficacy of
TNP-470 (a semisynthetic analogue of
fumagillin),
ovalicin, and eight
ovalicin derivatives.
TNP-470,
ovalicin, and three of the
ovalicin derivatives inhibited both E. intestinalis and V. corneae replication by more than 70% in vitro. Another three of the
ovalicin derivatives inhibited one of the two microsporidian species by more than 70%. None of the treated athymic mice survived the V. corneae
infection, but they did survive statistically significantly longer than the untreated controls after daily treatment with
fumagillin administered at 5, 10, and 20 mg/kg of
body weight subcutaneously (s.c.),
TNP-470 administered at 20 mg/kg intraperitoneally (i.p.), or
ovalicin administered at 5 mg/kg s.c. Of two
ovalicin derivatives that were assessed in vivo, NSC 9665 given
at 10 mg/kg i.p. daily also statistically significantly prolonged survival of the mice. No lesions associated with
drug toxicity were observed in the kidneys or livers of uninfected mice treated with these drugs at the highest dose of 20 mg/kg daily. These results thus support continued studies to identify more effective
fumagillin-related drugs for treating
microsporidiosis.