Intestinal microsporidiosis fumagillin
The parasitic disease intestinal microsporidiosis, caused by Enterocytozoon bieneusi, causes chronic diarrhoea, malabsorption and wasting in immunocompromised patients, including those with HIV infection, and there is currently no effective treatment. Sanofi-Synthelabo is investigating fumagillin as a potential treatment for the disease.
In a dose escalation trial designed to assess the safety and efficacy of oral fumagillin in the infection, 29 HIV positive patients with E. bieneusi infection were consecutively enrolled in the trial.1 Oral doses of the drug were given to four groups of patients for 14 days, in doses of 10, 20, 40 and 60mg a day for 14 days, and the efficacy and safety were evaluated after one, two, four and six weeks. Efficacy was assessed primarily by the clearance of microsporidia from stools, and follow-up duodenal biopsies. A total of 21 of the 29 patients transiently cleared microsporidia from their stools during the study. By the sixth week, all the patients given the three lower doses had a parasitic relapse. However, eight of the 11 patients given the 60mg dose apparently cleared microsporidia from their intestinal tracts and gained weight. No parasitic relapse was seen in these patients after 11.5 months.
In a randomised, double blind, placebo-controlled trial, 60mg oral fumagillin was given daily for two weeks to 12 immunocompromised patients with intestinal microsporidiosis.2 Ten of the subjects had HIV infection, and the remaining two had received organ transplants. All six who were given the active experienced clearance of the microsporidia, compared with none of the six given placebo.
Three given fumagillin experienced neutropenia and thrombocytopenia. All six of the controls subsequently had their infection cleared by open label treatment with fumagillin.
Phase III trials continue, and the drug looks as though it may be a promising therapy for this unpleasant and currently untreatable disease.