Leishmaniasis, Chagas disease and sleeping sickness are transfusion-transmitted diseases. These diseases affect more than 20 million people annually in Latin America, Asia and Africa, and each is caused by an infection acquired from a type of kinetoplastid parasite. Currently, treatment options for these diseases are expensive and have negative side-effects. Researchers at the Genomics Institute of the Novartis Research Foundation screened over 3 million compounds in proliferation assays using all three parasites. They identified and refined a compound called GNF6702, which selectively inhibits all three kinetoplastid proteasomes but does not affect the growth of mammalian cells. The compound is also well tolerated in mice. This new drug is currently undergoing further evaluation including toxicity testing. This drug may lead to a new class of therapeutics and also potentially could reduce the risk of transmission by transfusion for these parasitic infections.
- Khare S, Nagle AS, Biggart A, Lai YH, Liang F, Davis LC, Barnes SW, Mathison CJ, Myburgh E, Gao MY, Gillespie JR, Liu X, Tan JL, Stinson M, Rivera IC, Ballard J, Yeh V, Groessl T, Federe G, Koh HX, Venable JD, Bursulaya B, Shapiro M, Mishra PK, Spraggon G, Brock A, Mottram JC, Buckner FS, Rao SP, Wen BG, Walker JR, Tuntland T, Molteni V, Glynne RJ, Supek F. Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature 2016.