Primetime is collaborating with Dr. Osnat Herzberg of IBBR-University of Maryland for the development of treatment to combat giardiasis resistant to standard care drugs. Giardia lamblia is a highly infective waterborne parasite that causes severe diarrhea. Current antigiardiasis drugs fail at about 20% of the cases and they all have undesirable side effects. Additionally, drug-resistant G. lamblia strains can be readily raised in the laboratory, increasing the risk of this category B bioterrorism organism. Chronic infection of giardiasis and lack of treatment in poor countries lead to malnutrition, growth retardation in children, and death. The prevalence of giardiasis impacts global health profoundly and World Health Organization’s has included giardiasis in its Neglected Diseases Initiative.
Screening an approved drug library, we have discovered that Fumagillin kills Giardia trophozoites in vitro with high potency. Fumagillin is an orphan drug used in the European Union to treat intestinal microsporidiosis in immune compromised patients. We followed these assays by in vivo studies in mice, confirming the efficacy and excellent therapeutic index of Fumagillin. In human and the malaria parasite, Fumagillin has been shown to selectively inhibit methionine aminopeptidase 2 (MetAP-2) but not methionine aminopeptidase 1 (MetAP- 1). Organisms that produce only the MetAP-2, mostly bacteria and also G. lamblia, require this enzyme for survival. None of the currently used drugs to treat giardiasis act on this enzyme. Thus, Fumagillin will not be subject to the current drug resistance mechanisms that result in treatment failures. We are optimizing Fumagillin lead for treatment of giardiasis.