Efficacy of the fumagillin analog TNP-470 for Nucleospora salmonis and Loma salmonae infections in chinook salmon Oncorhynchus tshawytscha

Higgins, M. J.; Kent, Michael L.; Moran, J. D. W.; Weiss, Louis M.; Dawe, S. C.

doi:10.3354/dao034045

Cited by 34 publications

(21 citation statements)

References 1 publication

(2 reference statements)

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“…TNP-470 and FOS68, inhibit the in vitro growth of Encephalitozoon hellem, E. cuniculi, E. intestinalis and other microsporidia at concentrations as low as 3 nM (Didier 1997, Didier et al 1998, Coyle et al 1998, Weiss et al 2001). In addition, both fumagillin and TNP-470 have demonstrated activity in murine and fish models of microsporidiosis (Coyle et al 1998, Higgins et al 1998. Fumagillin has also been demonstrated to have efficacy in human infection with E. hellem (ocular disease) and E. bieneusi (intestinal disease) (Molina et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Several laboratories have demonstrated in vitro that this drug has activity against both Encephalitozoonidae and Vittaforma corneae (Shadduck 1980, Franssen et al 1995, Didier 1997, Coyle et al 1998. TNP-470, a fumagillin derivative developed as an anti-angiogenesis drug, is active both in vitro and in vivo against several microsporidia (Coyle et al 1998, Higgins et al 1998. Fumagillin has been demonstrated to have efficacy for the treatment of diarrhoea due to E. bieneusi in AIDS patients (Molina et al 2002).…”

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confidence: 99%

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Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis

Zhang¹,

Huang²,

Cali³

et al. 2005

FOLIA PARASIT

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Abstract. The Microsporidia have been reported to cause a wide range of clinical diseases particularly in patients that are immunosuppressed. They can infect virtually any organ system and cases of gastrointestinal infection, encephalitis, ocular infection, sinusitis, myositis and disseminated infection are well described in the literature. While benzimidazoles such as albendazole are active against many species of Microsporidia, these drugs do not have significant activity against Enterocytozoon bieneusi. Fumagillin, ovalicin and their analogues have been demonstrated to have antimicrosporidial activity in vitro and in animal models of microsporidiosis. Fumagillin has also been demonstrated to have efficacy in human infections due to E. bieneusi. Fumagillin is an irreversible inhibitor of methionine aminopeptidase type 2 (MetAP2). Homology cloning employing the polymerase chain reaction was used to identify the MetAP2 gene from the human pathogenic microsporidia Encephalitozoon cuniculi, Encephalitozoon hellem, Encephalitozoon intestinalis, Brachiola algerae and E. bieneusi. The full-length MetAP2 coding sequence was obtained for all of the Encephalitozoonidae. Recombinant E. cuniculi MetAP2 was produced in baculovirus and purified using chromatographic techniques. The in vitro activity and effect of the inhibitors bestatin and TNP-470 on this recombinant microsporidian MetAP2 was characterized. An in silico model of E. cuniculi MetAP2 was developed based on crystallographic data on human MetAP2. These reagents provide new tools for the development of in vitro assay systems to screen candidate compounds for use as new therapeutic agents for the treatment of microsporidiosis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis

Zhang¹,

Huang²,

Cali³

et al. 2005

FOLIA PARASIT

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“…It has also been demonstrated that TNP-470 is highly active against Encephalitozoon cuniculi and Encephalitozoon hellem , both in vitro and in vivo (Coyle and others 1998). Additionally, TNP-470 was found to inhibit the replication of N salmonis and L salmonae in salmonid fish (Higgins and others 1998). …”

Section: Introductionmentioning

confidence: 99%

Development of a novel in vitro method for drug development for fish; application to test efficacy of antimicrosporidian compounds

et al. 2014

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Few drugs are approved for treating diseases caused by parasites in minor species such as fish. This is due, in part, to the expense of drug development and to the comparatively small market. In vivo effectiveness trials for antiparasitic drugs are costly, time consuming and require ethics approval, therefore an in vitro screening approach is a cost-effective alternative to finding promising drug candidates. We developed an in vitro testing system to test antimicrosporidial compounds against a microsporidian pathogen Heterosporis saurida. Five antiparasitic compounds, albendazole, fumagillin, TNP-70, nitazoxanide and lufenuron, were assayed for antimicrosporidial activity. All compounds reduced the number of H saurida spores in infected cells when applied at a concentration that did not appear to be toxic to the host cells. Albendazole inhibited replication of H saurida by >60 per cent, fumagillin and its analogue TNP-470 inhibited H saurida >80 per cent, nitazoxanide and lufenuron inhibited growth >70 per cent. The data suggest that both fumagillin and its analogous TNP-70 hold the best promise as therapeutic agents against H saurida. The ability to use fish cell cultures to assess drugs against H saurida demonstrates an approach that may be helpful to evaluate other drugs on different microsporidia and host cells.

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“…Four species, Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon hellem , and Encephalitozoon cuniculi , are responsible for causing the majority of microsporidian infections in humans [16,17]. Fumagillin and related compounds such as TNP‐470 and ovalicin appear to be among the most effective drug for treating microsporidiosis [4,5,8,9,16,17,20,21]. Fumagillin, TNP‐470, and ovalicin also inhibit angiogenesis by covalently binding to methionine aminopeptidase 2 (MetAP2) in endothelial cells [7,10,18,22].…”

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confidence: 99%

Methionine Aminopeptidase 2 Expression in Microsporidia

Didier

Martin

Stovall

et al. 2003

J Eukaryotic Microbiology

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Efficacy of the fumagillin analog TNP-470 for Nucleospora salmonis and Loma salmonae infections in chinook salmon Oncorhynchus tshawytscha

Cited by 34 publications

References 1 publication

Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis

Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis

Development of a novel in vitro method for drug development for fish; application to test efficacy of antimicrosporidian compounds

Methionine Aminopeptidase 2 Expression in Microsporidia

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