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Experimental Drug May Be Universal Cure for Kinetoplastid-Based Diseases

By LabMedica International staff writers
Posted on 17 Aug 2016
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Image: Trypanosoma sp. parasites in blood smear from a patient with African trypanosomiasis (Photo courtesy of the CDC).
Image: Trypanosoma sp. parasites in blood smear from a patient with African trypanosomiasis (Photo courtesy of the CDC).
An experimental drug that targets the kinetoplast proteasome found in several types of protozoan parasites shows potential for development into a universal treatment for these pathogenic microorganisms.

Chagas disease, leishmaniasis, and sleeping sickness affect some 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured by treatment to block the activity of a conserved parasite target. However, no such molecular targets or broad-spectrum drugs have been identified to date.

A significant advance in the search for a drug to treat kinetoplastid parasite infections was described in the August 8, 2016, online edition of the journal Nature. Investigators from several British research institutes in collaboration with the Novartis Research Foundation (San Diego, CA, USA) and the Wellcome Trust (United Kingdom) evaluated the experimental drug GNF6702, which had been discovered during a screen of more than three million compounds by the Genomics Institute of the Novartis Research Institute.

The investigators reported that GNF6702 demonstrated unprecedented in vivo efficacy by clearing parasites from mice in all three models of infection. GNF6702 inhibited the kinetoplastid proteasome through a non-competitive mechanism, did not inhibit the mammalian proteasome or growth of mammalian cells, and was well tolerated in mice.

Senior author Dr. Frantisek Supek, a biotechnology researcher at the Novartis Research Foundation, said, "We found that these parasites harbor a common weakness. We hope to exploit this weakness to discover and develop a single class of drugs for all three diseases."

Dr. Stephen Caddick, director of innovation at the Wellcome Trust, said, "These three diseases lead to more than 50,000 deaths annually, yet they receive relatively little funding for research and drug development. We hope that our early stage support for this research will provide a basis for the development of new treatments that could reduce suffering for millions of people in the poorest regions of the world."

Related Links:
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Wellcome Trust
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